Modified antisense oligonucleotide, free and / or nanostructured, compositions, methods and use for plant disease control.

Description

/ 27 Modified antisense oligonucleotide, free and / or nanostructured, compositions, methods and use for plant disease control. Field of invention

[001] The present invention belongs to the green patent technical sector and represents a sustainable agriculture technology focused on improving soil and the environment, since the use of the developed technology will result in a reduction in the application of agrochemicals to plants. It also belongs to the technical sector of plant biotechnology, plant protection, and genetic control of agricultural diseases. The invention can also be applied in the sectors of plant defense technologies based on gene silencing. More specifically, the invention refers to the development and use of chemically modified antisense oligonucleotides (ASOs), free or nanostructured, for silencing susceptibility genes, aiming at controlling plant diseases caused by bacteria, fungi, oomycetes, and viruses. Thus, the present invention proposes the application of ASOs to decrease the activation of susceptibility genes, minimizing the damage caused by phytopathogens.The technology can be applied to various plant species, since susceptibility genes are conserved in different plants. The methods developed can be used for the prevention or treatment of infected plants. Fundamentals of the invention

[002] The tomato (Solanum lycopersicum L.) is a vegetable native to the South American Andes that was domesticated in Mexico and subsequently distributed to other continents (Bai & Lindhout 2007, Domestication and breeding of tomatoes: what have we gained and what can we gain in the future? Ann Bot 2007; 100:1085-1094. https: / / doi.org / 10.1093 / aob / mcm150). The plants have a wide climatic tolerance and are cultivated in tropical and temperate regions worldwide. Tomato cultivation is present in more than 169 countries, totaling 186.8 million tons produced on more than 5 million hectares, considered the second most cultivated vegetable in the world, surpassed only by the potato (FAOSTAT 2024, Petition 870260017816, dated 25 / 02 / 2026, page 5 / 45 / 27 Harvested area, yield and production in the main tomato-producing countries. http: / / faostat.fao.org. Accessed 15 April 2024). Brazilian production in 2023 was 3,915,209 million tons and the average productivity was 70.20 tons / ha, making the country the eighth largest producer in the world (FAOSTAT 2024, Harvested area, yield and production in the main tomato-producing countries. Available at:<http: / / faostat.fao.org> ; IBGE 2024, IBGE Systematic Survey of Agricultural Production, Statistics on Agricultural Production. Brasília).

[003] The largest national producers are the states of São Paulo and Goiás, responsible for 26.55% and 26.26% of production, respectively. In São Paulo, productivity was 83.86 kg / ha, with the majority being staked tomatoes destined for fresh consumption. In Goiás, most of the production is of ground tomatoes, grown under irrigation, with an estimated average productivity of 77.7 kg / ha, this production being destined for the pulp industries (IBGE, 2024). Intensive tomato production has increased crop productivity, although costs such as fertilization, irrigation, pest control, and cultural practices have also been higher (IBGE 2024, IBGE Systematic Survey of Agricultural Production Statistics of Agricultural Production. Brasília). Several factors can limit tomato production, such as unbalanced fertilization, lack of soil moisture or excess moisture, strong winds, and the occurrence of pests and diseases.Lopes et al (2021) report several pathogens that cause diseases in tomato plants, and among the most important for the crop are bacteria of the genus Xanthomonas.

[004] Xanthomonas euvesicatoria pv. perforans, X. euvesicatoria pv. euvesicatoria, X. vesicatoria and X. hortorum pv. gardineri are considered the causal agents of bacterial spot of tomato (BSB) and are widely distributed throughout the world. In Brazil, there are reports of the presence of three species infecting tomato plants, and the most prevalent are X. euvesicatoria pv. perforans and X. hortorum pv. gardineri, which can lead to losses of around 40% of production (Quezado-Duval et al. 2014, https: / / doi.org / 10.1590 / S0102-053620140000400012; Araújo et al. 2017, https: / / doi.org / 10.1111 / ppa.12543). The occurrence of bacterial spot is favored by relative humidity between 95% and 100% and temperatures between 22°C and 28°C. However, Araújo et al (2011) demonstrated that X. hortorum pv. gardineri develops better in Petition 870260017816, dated 25 / 02 / 2026, page 6 / 45 / 27 locations with temperatures of 20°C, while X. euvesicatoria pv. perforans has greater adaptability in locations with temperatures of 30°C (https: / / doi.org / 10.17660 / ActaHortic.2011.914.3).

[005] The severity of the disease can be increased when rainfall occurs in conjunction with strong winds and in sprinkler irrigation systems. These are factors that increase the spread of the bacteria, due to the impact of water droplets on the leaves, since the bacterial cells are dislodged and form contaminated droplets, which are transported by the wind (Quezado-Duval & Lopes 2010, Bacterial spot: an update for the integrated production system of industrial tomatoes). Other modes of dissemination of the bacteria occur through infected seedlings and seeds, pruning and harvesting tools, or by humans themselves. In addition, weeds and crop residues have been important sources of inoculum, due to the ability of the bacteria to survive in infected material when there is no susceptible host present (Newberry et al. 2019, https: / / doi.org / 10.1128 / AEM.00885-19).

[006] Upon contact with plant tissue, the bacterium infects through stomata or wounds and reaches the apoplast, followed by growth in the substomatal chamber and multiplication in the intercellular spaces (Potnis et al. 2015, https: / / doi.org / 10.1111 / mpp.12244). As a consequence of infection, irregular lesions appear, which become dark brown to black, with a water-soaked appearance under high humidity conditions, and may present yellowish halos. In some cases of infection by X. euvesicatoria pv. perforans, the symptom of "shot hole" may occur, due to the decay of dead tissue in the center of the lesion. With the progression of symptoms under ideal conditions for the pathogen, coalescence of the lesions may occur, resulting in extensive necrosis and drying of the leaves, which favors sunburn of the fruits. In addition to symptoms on the leaves, the bacteria is capable of infecting other parts of the plant, such as stems, fruits, petals, and flowers.

[007] MBT management focuses primarily on cultural practices such as the use of healthy seeds and seedlings, elimination of tomato and pepper crop residues and volunteer plants that may be secondary hosts, as well as the use of crop rotation. Petition 870260017816, dated 02 / 25 / 2026, page 7 / 45 / 27 crops with non-host species. Chemical control of the disease has been carried out with copper-based products, resistance inducers such as acibenzolar-S-methyl, with antibiotics, such as kasugamycin, and with plant extracts and polysaccharides (MAPA 2022, Phytosanitary Pesticide System - AGROFIT. Available at:<https: / / agrofit.agricultura.gov.br / agrofit_cons / principal_agrofit_cons> ).

[008] In this sense, host resistance has been one of the main objectives of tomato breeding programs, however, there are still no resistant cultivars for the control of bacterial spot (Potnis et al. 2015, Bacterial spot of tomato and pepper: diverse Xanthomonas species with a wide variety of virulence factors posing a worldwide challenge. Molecular Plant Pathology 16:907-920. (https: / / doi.org / 10.1111 / mpp.12244). Conventional resistance mediated by resistance genes (R) has several limitations because it depends on interactions between the avirulence gene and the product of the R gene, and may be inefficient even before the implementation of a resistant cultivar in the field, as bacteria can acquire new effectors that prevent recognition by the R gene, leading to disease in the plant (Gassmann et al. 2000).

[009] An alternative strategy to the use of resistance genes is the silencing or knockout of susceptibility genes (S genes). S genes can act in different ways to favor the colonization of pathogens in the host (van Schie et al., 2014, Susceptibility genes 101: how to be a good host. Annu Rev Phytopathol. 2014; 52:551-81. doi: 10.1146 / annurev-phyto-102313-045854).

[0010] An innovative approach that has been explored involves the use of antisense DNA molecules to achieve gene silencing. In this approach, antisense oligonucleotides (ASOs) containing chemical modifications are used, targeting susceptibility genes in the plant or virulence genes in the pathogen. ASOs are short (approximately 20 bp) single-stranded polymers of DNA or RNA, synthesized in vitro, that regulate gene expression by specific sequence binding to an RNA target, which is recognized by the RNaseH enzyme that promotes the cleavage of the mRNA strand. Chemical modifications, for example, of the phosphorothioate type, confer high stability in the cellular environment, preventing degradation by Petition 870260017816, dated 25 / 02 / 2026, page 8 / 45 / 27 plant nuclease enzymes (e.g., phosphatases). In this way, this methodology presents important advantages over the use of dsRNAs.

[0011] ASO-based technology has been primarily used in the medical field (Geary et al., 2015; Chery, 2016) with some studies focused on agricultural pest control or plant applications (de Lima et al. 2024, doi: 10.1094 / PHYTO02-24-0058-KC; Dinç et al., 2011, https: / / doi.org / 10.1104 / pp.111.185462; Oberemok et al., 2018, doi:10.3390 / molecules23061302; Oberemok et al., 2019, doi:10.1038 / s41598019-42688-8; Souza et al., 2023, doi:10.1016 / j.pmpp.2023.102163; Lambertucci et al., 2019, doi: 10.3389 / fpls.2019.01138; Távora et al., 2021, doi:10.1016 / j.jprot.2021.104223).

[0012] Recently, patent WO2024 / 100038 was filed, which targets plant pathogen genes. In the present invention, the target genes are from the plant and have no specificity, and therefore may result in resistance to other pathogens. Product regulation is simpler since it is not characterized as an agrochemical (which targets the pathogen).

[0013] ASO modifications can be classified into 3 generations (Mansoor & Melendez, 2008, Advances in antisense oligonucleotide development for target identification, validation, and as novel therapeutics. Gene Regul Syst Biol, 2008; 2, 275-295). In first-generation ASOs, the phosphate backbone linking the nucleotides is modified. One of the non-bridged oxygen atoms in the phosphodiester bond is replaced by a sulfur, methyl, or amine group, generating phosphorothioates (PS), methylphosphonates, and phosphoramidates, respectively. These modifications activate RNase H, resulting in the degradation of the target mRNA molecule.

[0014] The second generation of ASOs is characterized by alkylated modifications at the 2' position of ribose. The introduction of an oxygenated group leads to the formation of 2'-O-methyl (2'-OME) and 2'-O-methoxyethyl (2'-MOE) nucleotides. In these modifications, there is no recruitment of RNase H. The third generation is more heterogeneous and includes numerous modifications, the most common being blocked nucleic acids (LNAs), corresponding to a methylene bridge connecting the 2'-oxygen and the 4'-carbon of ribose; morpholino phosphorodiamidate oligomers (PMOs), in which ribose is Petition 870260017816, dated 25 / 02 / 2026, p. 9 / 45 / 27 replaced by a morpholine portion and the phosphodiester linkage by a phosphorodiamidate linkage; and peptide nucleic acids (PNAs), in which the ribosephosphate structure is replaced by a polyamide structure consisting of repeats of N-(2-aminotyl)glycine units, to which the bases are attached. ASOs with these modifications also do not result in the recruitment of RNAse H.

[0015] The biggest obstacle to the successful use of this tool concerns its absorption (cellular internalization) and durability. Consequently, the development of more efficient delivery methods is of great importance to ensure greater efficiency in gene silencing and to enable the development of products, such as nanoformulations. In this context, the ability of nanoparticles to penetrate biological membranes has led to the development of nanocarriers, initially focused mostly on animal cells and more recently on plant cells.

[0016] Nanoparticle-based delivery methods have significant advantages such as low cytotoxicity and broad applicability to a variety of plant species. Furthermore, nanoencapsulated molecules are protected from enzymatic degradation in biological environments and can be released in a controlled manner to target specific organelles or tissues. Thus, the combination of gene silencing strategies with nanotechnology allows the development of nanoformulations that can exhibit high efficiency and low toxicity to living organisms and the environment, representing an important approach for pest control (Mitter et al., 2017, Clay nanosheets for topical delivery of RNAi for sustained protection against plant viruses. Nature Plants 2017; 3: 16207 https: / / doi.org / 10.1038 / nplants.2016.207).

[0017] This invention offers a strategy for controlling plant diseases, such as bacterial spot of tomato, through the use of modified antisense oligodeoxynucleotides active in silencing susceptibility genes. One well-studied S gene is Downy Mildew Resistance 6 (DMR6), studied in Arabidopsis thaliana (Zeilmaker et al., 2015, DOWNY MILDEW RESISTANT 6 and DMR6-LIKE OXYGENASE 1 are partially redundant but distinct suppressors of immunity in Arabidopsis. Plant J. 2015; 81(2):210-22. doi: 10.1111 / tpj.12719), which regulates Petition 870260017816, dated 25 / 02 / 2026, page 10 / 45 / 27 negatively affects the defense responses of different hosts, favoring bacteria, oomycetes, and fungi, including in tomato (Thomazella et al. 2021, Loss of function of a DMR6 ortholog in tomato confers broad-spectrum disease resistance. Proc Natl Acad Sci USA 2021; 6:118(27):e2026152118. doi: 10.1073 / pnas.2026152118). Salicylic acid (SA) is a fundamental hormone for the defense response in plants.

[0018] The DMR6 gene has been reported as a disease susceptibility factor in Arabidopsis; however, its biochemical mechanism remains poorly understood. Thomazella et al. 2021 (Loss of function of a DMR6 ortholog in tomato confers broadspectrum disease resistance. Proc Natl Acad Sci USA 2021; 6:118(27):e2026152118. doi: 10.1073 / pnas.2026152118) demonstrated that knocking out the DMR6 gene resulted in a decrease in MBT symptoms, since the regulation of AS levels in vegetative plant tissues was altered during infection by the pathogen. However, the knockout resulted in a decrease in fruit size. Thus, gene silencing could be considered an alternative for obtaining plant resistance without undesirable pleiotropic effects, such as reduced fruit size.The DMR6 gene has also been reported as being involved in susceptibility to other plant diseases such as late blight caused by Phytophthora infestans (Pirrello et al., 2022, Grapevine DMR6-1 is a candidate gene for susceptibility to downy mildew. Biomolecules 2022; 12: 182. https: / / doi.org / 10.3390 / biom12020182), downy mildew caused by Hyaloperonospora arabidopsidis, bacterial spot caused by Pseudomonas syringae, and fruit rot caused by Pseudomonas capsici (Zeilmaker et al., 2015, DOWNY MILDEW RESISTANT 6 and DMR6-LIKE OXYGENASE 1 are partially redundant but distinct suppressors of immunity in Arabidopsis. Plant J. 2015; 81(2):210-22. doi: 10.1111 / tpj.12719).

[0019] Another reported S gene refers to the LIN6 invertase. Host plant sugars play a central role in plant-pathogen interactions (Rojas et al., 2014, Regulation of primary plant metabolism during plant-pathogen interactions and its contribution to plant defense. Frontiers in Plant Science 2014; 5: 1-12.). It is believed that the main soluble sugars, such as sucrose, glucose, and fructose, are involved in both the production and regulation of antifungal metabolites and in the maintenance of cellular homeostasis, and may also be used as a substrate for Petition 870260017816, dated 25 / 02 / 2026, page 11 / 45 / 27 the growth of pathogens (Morkunas and Ratajczak, 2014, The role of sugar signaling in plant defense responses against fungal pathogens. Acta Physiologiae Plantarum 2014; 36: 1607-1619.).

[0020] The machinery of the host cell is manipulated by many pathogens for nutrient release (Fatima and Senthil-Kumar, 2015, Plant and pathogen nutrient acquisition strategies. Front Plant Sci 2015; 6: 1-12. Oliva and Quibod, 2017, Immunity and starvation: new opportunities to elevate disease resistance in crops. Current Opinion in Plant Biol 2017; 38: 84-91). One of these alterations involves increased activity of cell wall invertases (Berger et al., 2007, Plant physiology meets phytopathology: plant primary metabolism and plant-pathogen interactions. J Exp Bot 2007; 58: 4019-4026; Bolton, 2009, Primary metabolism and plant defense — fuel for the fire. Mol PlantMicrobe Interact 2009; 22: 487-497; Proels and Hückelhoven, 2014, Cell-wall invertases, key enzymes in the modulation of plant metabolism during defense responses. Mol Plant Pathol 2014; 15: 858-864.) altering sucrose synthase at different levels.It has been shown that the use of hormones involved in the plant stress response pathway, abscisic acid and methyl jasmonate, resulted in the induction of LIN6 promoter expression, reinforcing the idea that this gene is linked to plant defense pathways (Proels & Roitsch, 2009, Extracellular invertase LIN6 of tomato: a pivotal enzyme for integration of metabolic, hormonal, and stress signals is regulated by a diurnal rhythm. J Exp Bot, 2009; 60: 1555-67).

[0021] Kocal et al. (Cell wall-bound invertase limits sucrose export and is involved in symptom development and photosynthesis inhibition during compatible interaction between tomato and Xanthomonas campestris pv vesicatoria. Plant Physiol 2008; 148: 1523-36) observed that silencing LIN6 and LIN8 resulted in pathogenicity gene repression (PR) and decreased symptoms after infection with Xanthomonas campestris pv. vesicatoria in tomato plants. Recently, Lacrampe et al., 2020 (Regulation of sugar metabolism genes in nitrogen-dependent susceptibility of tomato stems to Botrytis cinerea. Ann Bot. 2021; 127(1):143-154. doi: 10.1093 / aob / mcaa155) reported the involvement of tomato invertases (Sl-LIN5 to Sl-LIN9) in the susceptibility of tomato to Botrytis cinerea. Petition 870260017816, dated 25 / 02 / 2026, p. 12 / 45 / 27

[0022] In the present invention, ASOs were selected to repress susceptibility genes and reduce symptoms caused by phytopathogens in plants. The effect of ASOs on plant protection was verified after different inoculation assays with the pathogen, confirming the reduction of symptoms and repression of target genes. Subsequently, the nanoformulation of ASOs was carried out, and although statistical validation was not possible, it was observed that the action of nanostructured ASOs was superior to free ASOs, potentially resulting in a considerable reduction in the costs of the technology. Based on the results obtained, we demonstrate that the use of Antisense Oligonucleotides (ASOs) is a promising and sustainable strategy within the Innovative Precision Breeding Technologies (TIMPs) approach for pest control in plants.Furthermore, according to in silico analyses, the ASO sequence is specific to the plant's target genes and, therefore, should not have any effect on non-target organisms. Brief description of the Figures Figure 1. Analysis of Tomato Bacterial Spot (TBS) symptoms in tomato leaves treated with ASO-DMR6 10 μM. A. Tomato leaves showing the evolution of TBS symptoms with ASO-DMR6 treatment compared to its control (Random), 12 and 15 days after inoculation (dai). B. Quantification of the symptomatic area using ImageJ software. Asterisks represent a significant difference using the Student's t-test (P<0.05). Figure 2. Analysis of Tomato Bacterial Spot (TBS) symptoms in tomato leaves treated with ASO-LIN6 10 μM. A. Tomato leaves showing the evolution of TBS symptoms with the ASO-LIN6 treatment compared to its control (Random), 12 and 15 days after inoculation (dai). B. Quantification of the symptomatic area using ImageJ software. Asterisks represent a significant difference using the t-student test (P<0.05). Figure 3. Evaluation of MTB symptoms after infiltration of free ASO-DMR6 10 μM. A. Tomato leaves demonstrating the evolution of MTB symptoms with the ASO-DMR6 treatment compared to its control (Random) and with the salicylic acid analog (ASA) acibenzolar-S-methyl, 20 days after inoculation (dai). B. Quantification of Petition 870260017816, dated 25 / 02 / 2026, page 13 / 45 / 27 symptomatic area using ImageJ software. Asterisks represent a significant difference using the Mann-Whitney test (P<0.05). Figure 4. Evaluation of symptoms of bacterial spot of tomato (MBT) after infiltration of ASO-DMR6 and ASO-LIN6 1 μM. A. Tomato leaves demonstrating the evolution of MTB symptoms with the ASO-DMR6 and ASO-LIN6 treatments compared to their control (Random), 20 days after inoculation (dai). B. Quantification of the symptomatic area using ImageJ software. Asterisks represent a significant difference using the Mann-Whitney test (P<0.05). Figure 5. Evaluation of symptoms of bacterial spot of tomato (MBT) after infiltration of free or nanostructured ASO-DMR6. Quantification of the symptomatic area using ImageJ software. Asterisks represent a significant difference using the Mann-Whitney test (P<0.05). Figure 6. Evaluation of symptoms of bacterial spot of tomato (MBT) after infiltration of Nano-DMR6 (1 μM), Nano-LIN6 (1 μM) and Nano-vazia. A. Tomato leaves demonstrating the evolution of MTB symptoms with the NanoDMR6 and Nano-LIN6 treatments compared to their control (Nano-vazia), 20 days after inoculation (dai). B. Quantification of the symptomatic area using ImageJ software. Asterisks represent a significant difference using the t-student test (P<0.05). Figure 7. Evaluation of symptoms of bacterial spot of tomato (MBT) after infiltration of ASO-DMR6, ASO-Random, at concentrations of 1 μM and 0.1 μM, and spraying of a salicylic acid analog (AAS) compound, 20 days after inoculation (dai). Quantification of the symptomatic area using QUANT software. Asterisks represent a significant difference using the t-student test (P<0.05). Figure 8. Evaluation of symptoms of bacterial spot of tomato (MBT) after infiltration of Nano-DMR6 (1 μM and 0.1 μM) and Nano-vazia and spraying of salicylic acid analog (SAA) 20 days after inoculation (dai). Quantification of the symptomatic area using QUANT software. Asterisks represent a significant difference using the t-student test (P<0.05). Petition 870260017816, dated 25 / 02 / 2026, page 14 / 45 / 27 Figure 9. Evaluation of symptoms of bacterial spot of tomato (MBT) after infiltration of Nano-LIN6 (1 μM and 0.1 μM) and Nano-vazia and spraying of a salicylic acid analog (SAA) compound 20 days after inoculation (dai). Quantification of the symptomatic area using QUANT software. Asterisks represent a significant difference using the t-student test (P<0.05). Figure 10. Analysis of the relative expression of the DMR6 gene in tomato plants. A. Plants treated with Nano-DMR6 [1 μM] compared with plants treated with Nanovazia. B. Plants treated with Nano-DMR6 [1 μM] compared with plants treated with Water. The red bars represent the gene that was negatively regulated; * symbol indicates statistical significance of gene expression (P<0.05). Description of the invention

[0023] The present invention relates to the development and use of modified antisense oligonucleotides, free or nanostructured, for gene silencing aimed at controlling plant diseases. More specifically, the invention relates to the development and use of chemically modified antisense oligonucleotides (ASOs), free or nanostructured, for silencing the DMR6 and LIN6 susceptibility genes, reducing damage caused by bacteria, fungi, oomycetes, and viruses. The active molecule is a single-stranded DNA nucleic acid that can be used for disease control in formulations such as a foliar spray.

[0024] The antisense sequence (ASO) is complementary to a part of a plant susceptibility gene, which causes the negative regulation of the target mRNA through the activation of the RNase H enzyme, leading to the silencing of said gene. The methods of the invention may have practical application in any area of ​​technology aimed at reducing damage caused by bacterial, fungal, oomycete, and viral diseases. The methods of the invention may also find practical application when the objective is to achieve the negative regulation of target genes. More specifically, the invention may have practical application, but is not limited to, 1. plant protection against diseases caused by pathogens, 2. protection of perishable material (such as food, seeds, etc.) against damage caused by phytopathogens, Petition 870260017816, dated 25 / 02 / 2026, p. 15 / 45 / 27 and in general in any application where damage caused by phytopathogens needs to be controlled.

[0025] The modified antisense oligonucleotides of the present invention are characterized by being constructed from the DMR6 (SEQ ID NO: 1) and / or LIN6 (SEQ ID NO: 2) genes.

[0026] The invention relates to modified antisense oligonucleotides whose sequence has at least 90%, more specifically 95%, more specifically 98%, more specifically 99% sequence similarity with any of the sequences described: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO:106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO:116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, Petição 870260017816, de 25 / 02 / 2026, pág. 16 / 45 / 27 SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO 122, SEQ ID NO 127, SEQ ID NO 132, SEQ ID NO 137, SEQ ID NO 142, SEQ ID NO 147, SEQ ID NO 152, SEQ ID NO 157, SEQ ID NO 162, SEQ ID NO 167, SEQ ID NO 172, SEQ ID NO 177, SEQ ID NO 182, SEQ ID NO 187, SEQ ID NO 192, SEQ ID NO 197, SEQ ID NO 202, SEQ ID NO 207, SEQ ID NO 212, SEQ ID NO 217, SEQ ID NO 222, SEQ ID NO 227, SEQ ID NO 232, SEQ ID NO 237, SEQ ID NO 242, SEQ ID NO 247, SEQ ID NO 252, SEQ ID NO 257, SEQ ID NO 262, SEQ ID NO 267, SEQ ID NO 272, SEQ ID NO 277, SEQ ID NO 123, SEQ ID NO 128, SEQ ID NO 133, SEQ ID NO 138, SEQ ID NO 143, SEQ ID NO 148, SEQ ID NO 153, SEQ ID NO 158, SEQ ID NO 163, SEQ ID NO 168, SEQ ID NO 173, SEQ ID NO 178, SEQ ID NO 183, SEQ ID NO 188, SEQ ID NO 193, SEQ ID NO 198, SEQ ID NO 203, SEQ ID NO 208, SEQ ID NO 213, SEQ ID NO 218, SEQ ID NO 223, SEQ ID NO 228, SEQ ID NO 233, SEQ ID NO 238, SEQ ID NO 243, SEQ ID NO 248, SEQ ID NO 253, SEQ ID NO 258, SEQ ID NO 263, SEQ ID NO 268, SEQ ID NO 273, SEQ ID NO 278, SEQ ID NO 124, SEQ ID NO 129, SEQ ID NO 134, SEQ ID NO 139, SEQ ID NO 144, SEQ ID NO 149, SEQ ID NO 154, SEQ ID NO 159, SEQ ID NO 164, SEQ ID NO 169, SEQ ID NO 174, SEQ ID NO 179, SEQ ID NO 184, SEQ ID NO 189, SEQ ID NO 194, SEQ ID NO 199, SEQ ID NO 204, SEQ ID NO 209, SEQ ID NO 214, SEQ ID NO 219, SEQ ID NO 224, SEQ ID NO 229, SEQ ID NO 234, SEQ ID NO 239, SEQ ID NO 244, SEQ ID NO 249, SEQ ID NO 254, SEQ ID NO 259, SEQ ID NO 264, SEQ ID NO 269, SEQ ID NO 274, SEQ ID NO 279, SEQ ID NO 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, SEQ ID NO: 126, SEQ ID NO: 131, SEQ ID NO: 136, SEQ ID NO: 141, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 156, SEQ ID NO: 161, SEQ ID NO: 166, SEQ ID NO: 171, SEQ ID NO: 176, SEQ ID NO: 181, SEQ ID NO: 186, SEQ ID NO: 191, SEQ ID NO: 196, SEQ ID NO: 201, SEQ ID NO: 206, SEQ ID NO: 211, SEQ ID NO: 216, SEQ ID NO: 221, SEQ ID NO: 226, SEQ ID NO: 231, SEQ ID NO: 236, SEQ ID NO: 241, SEQ ID NO: 246, SEQ ID NO: 251, SEQ ID NO: 256, SEQ ID NO: 261, SEQ ID NO: 266, SEQ ID NO: 271, SEQ ID NO: 276, SEQ ID NO: 281, Petição 870260017816, de 25 / 02 / 2026, pág. 17 / 45 / 27 SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO 282, SEQ ID NO 287, SEQ ID NO 292, SEQ ID NO 297, SEQ ID NO 302, SEQ ID NO 307, SEQ ID NO 312, SEQ ID NO 317, SEQ ID NO 322, SEQ ID NO 327, SEQ ID NO 332, SEQ ID NO 337, SEQ ID NO 342, SEQ ID NO 347, SEQ ID NO 352, SEQ ID NO 357, SEQ ID NO 362, SEQ ID NO 367, SEQ ID NO 372, SEQ ID NO 377, SEQ ID NO 382, SEQ ID NO 387, SEQ ID NO 392, SEQ ID NO 397, SEQ ID NO 402, SEQ ID NO 407, SEQ ID NO 412, SEQ ID NO 417, SEQ ID NO 422, SEQ ID NO 427, SEQ ID NO 432, SEQ ID NO 437, SEQ ID NO 283, SEQ ID NO 288, SEQ ID NO 293, SEQ ID NO 298, SEQ ID NO 303, SEQ ID NO 308, SEQ ID NO 313, SEQ ID NO 318, SEQ ID NO 323, SEQ ID NO 328, SEQ ID NO 333, SEQ ID NO 338, SEQ ID NO 343, SEQ ID NO 348, SEQ ID NO 353, SEQ ID NO 358, SEQ ID NO 363, SEQ ID NO 368, SEQ ID NO 373, SEQ ID NO 378, SEQ ID NO 383, SEQ ID NO 388, SEQ ID NO 393, SEQ ID NO 398, SEQ ID NO 403, SEQ ID NO 408, SEQ ID NO 413, SEQ ID NO 418, SEQ ID NO 423, SEQ ID NO 428, SEQ ID NO 433, SEQ ID NO 438, SEQ ID NO 284, SEQ ID NO 289, SEQ ID NO 294, SEQ ID NO 299, SEQ ID NO 304, SEQ ID NO 309, SEQ ID NO 314, SEQ ID NO 319, SEQ ID NO 324, SEQ ID NO 329, SEQ ID NO 334, SEQ ID NO 339, SEQ ID NO 344, SEQ ID NO 349, SEQ ID NO 354, SEQ ID NO 359, SEQ ID NO 364, SEQ ID NO 369, SEQ ID NO 374, SEQ ID NO 379, SEQ ID NO 384, SEQ ID NO 389, SEQ ID NO 394, SEQ ID NO 399, SEQ ID NO 404, SEQ ID NO 409, SEQ ID NO 414, SEQ ID NO 419, SEQ ID NO 424, SEQ ID NO 429, SEQ ID NO 434, SEQ ID NO 439, SEQ ID NO 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, 440, SEQ ID NO: 286, SEQ ID NO: 291, SEQ ID NO: 296, SEQ ID NO: 301, SEQ ID NO: 306, SEQ ID NO: 311, SEQ ID NO: 316, SEQ ID NO: 321, SEQ ID NO: 326, SEQ ID NO: 331, SEQ ID NO: 336, SEQ ID NO: 341, SEQ ID NO: 346, SEQ ID NO: 351, SEQ ID NO: 356, SEQ ID NO: 361, SEQ ID NO: 366, SEQ ID NO: 371, SEQ ID NO: 376, SEQ ID NO: 381, SEQ ID NO: 386, SEQ ID NO: 391, SEQ ID NO: 396, SEQ ID NO: 401, SEQ ID NO: 406, SEQ ID NO: 411, SEQ ID NO: 416, SEQ ID NO: 421, SEQ ID NO: 426, SEQ ID NO: 431, SEQ ID NO: 436, SEQ ID NO: 441, Petição 870260017816, de 25 / 02 / 2026, pág. 18 / 45 / 27 SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO SEQ ID NO 442, SEQ ID NO 447, SEQ ID NO 452, SEQ ID NO 457, SEQ ID NO 462, SEQ ID NO 467, SEQ ID NO 472, SEQ ID NO 477, SEQ ID NO 482, SEQ ID NO 487, SEQ ID NO 492, SEQ ID NO 497, SEQ ID NO 502, SEQ ID NO 507, SEQ ID NO 512, SEQ ID NO 517, SEQ ID NO 522, SEQ ID NO 527, SEQ ID NO 532, SEQ ID NO 537, SEQ ID NO 542, SEQ ID NO 547, SEQ ID NO 552, SEQ ID NO 557, SEQ ID NO 562, SEQ ID NO 567, SEQ ID NO 572, SEQ ID NO 577, SEQ ID NO 582, SEQ ID NO 587, SEQ ID NO 592, SEQ ID NO 597, SEQ ID NO 443, SEQ ID NO 448, SEQ ID NO 453, SEQ ID NO 458, SEQ ID NO 463, SEQ ID NO 468, SEQ ID NO 473, SEQ ID NO 478, SEQ ID NO 483, SEQ ID NO 488, SEQ ID NO 493, SEQ ID NO 498, SEQ ID NO 503, SEQ ID NO 508, SEQ ID NO 513, SEQ ID NO 518, SEQ ID NO 523, SEQ ID NO 528, SEQ ID NO 533, SEQ ID NO 538, SEQ ID NO 543, SEQ ID NO 548, SEQ ID NO 553, SEQ ID NO 558, SEQ ID NO 563, SEQ ID NO 568, SEQ ID NO 573, SEQ ID NO 578, SEQ ID NO 583, SEQ ID NO 588, SEQ ID NO 593, SEQ ID NO 598, SEQ ID NO 444, SEQ ID NO 449, SEQ ID NO 454, SEQ ID NO 459, SEQ ID NO 464, SEQ ID NO 469, SEQ ID NO 474, SEQ ID NO 479, SEQ ID NO 484, SEQ ID NO 489, SEQ ID NO 494, SEQ ID NO 499, SEQ ID NO 504, SEQ ID NO 509, SEQ ID NO 514, SEQ ID NO 519, SEQ ID NO 524, SEQ ID NO 529, SEQ ID NO 534, SEQ ID NO 539, SEQ ID NO 544, SEQ ID NO 549, SEQ ID NO 554, SEQ ID NO 559, SEQ ID NO 564, SEQ ID NO 569, SEQ ID NO 574, SEQ ID NO 579, SEQ ID NO 584, SEQ ID NO 589, SEQ ID NO 594, SEQ ID NO 599, SEQ ID NO 445, 450, 455, 460, 465, 470, 475, 480, 485, 490, 495, 500, 505, 510, 515, 520, 525, 530, 535, 540, 545, 550, 555, 560, 565, 570, 575, 580, 585, 590, 595, 600, SEQ ID NO: 446, SEQ ID NO: 451, SEQ ID NO: 456, SEQ ID NO: 461, SEQ ID NO: 466, SEQ ID NO: 471, SEQ ID NO: 476, SEQ ID NO: 481, SEQ ID NO: 486, SEQ ID NO: 491, SEQ ID NO: 496, SEQ ID NO: 501, SEQ ID NO: 506, SEQ ID NO: 511, SEQ ID NO: 516, SEQ ID NO: 521, SEQ ID NO: 526, SEQ ID NO: 531, SEQ ID NO: 536, SEQ ID NO: 541, SEQ ID NO: 546, SEQ ID NO: 551, SEQ ID NO: 556, SEQ ID NO: 561, SEQ ID NO: 566, SEQ ID NO: 571, SEQ ID NO: 576, SEQ ID NO: 581, SEQ ID NO: 586, SEQ ID NO: 591, SEQ ID NO: 596, SEQ ID NO: 601, Petição 870260017816, de 25 / 02 / 2026, pág. 19 / 45 / 27 SEQ ID NO: 602, SEQ ID NO: 607, SEQ ID NO: 612, SEQ ID NO: 617, SEQ ID NO: 622, SEQ ID NO: 627, SEQ ID NO: 632, SEQ ID NO: 637, SEQ ID NO: 642, SEQ ID NO: 647, SEQ ID NO: 652, SEQ ID NO: 657, SEQ ID NO: 662, SEQ ID NO: 667, SEQ ID NO: 672, SEQ ID NO: 677, SEQ ID NO: 682, SEQ ID NO: 687, SEQ ID NO: 692, SEQ ID NO: 697, SEQ ID NO: 702, SEQ ID NO: 707, SEQ ID NO: 712, SEQ ID NO: 717, ID NO: 722, SEQ ID NO: 727, SEQ ID NO: 732, SEQ ID NO: 737, SEQ ID NO: 742, SEQ ID NO: 747, SEQ ID NO: 752, SEQ ID NO: 757, SEQ SEQ ID NO: 603, SEQ ID NO: 608, SEQ ID NO: 613, SEQ ID NO: 618, SEQ ID NO: 623, SEQ ID NO: 628, SEQ ID NO: 633, SEQ ID NO: 638, SEQ ID NO: 643, SEQ ID NO: 648, SEQ ID NO: 653, SEQ ID NO: 658, SEQ ID NO: 663, SEQ ID NO: 668, SEQ ID NO: 673, SEQ ID NO: 678, SEQ ID NO: 683, SEQ ID NO: 688, SEQ ID NO: 693, SEQ ID NO: 698, SEQ ID NO: 703, SEQ ID NO: 708, SEQ ID NO: 713, SEQ ID NO: 718, ID NO: 723, SEQ ID NO: 728, SEQ ID NO: 733, SEQ ID NO: 738, SEQ ID NO: 743, SEQ ID NO: 748, SEQ ID NO: 753, SEQ ID NO: 758, SEQ SEQ ID NO: 604, SEQ ID NO: 609, SEQ ID NO: 614, SEQ ID NO: 619, SEQ ID NO: 624, SEQ ID NO: 629, SEQ ID NO: 634, SEQ ID NO: 639, SEQ ID NO: 644, SEQ ID NO: 649, SEQ ID NO: 654, SEQ ID NO: 659, SEQ ID NO: 664, SEQ ID NO: 669, SEQ ID NO: 674, SEQ ID NO: 679, SEQ ID NO: 684, SEQ ID NO: 689, SEQ ID NO: 694, SEQ ID NO: 699, SEQ ID NO: 704, SEQ ID NO: 709, SEQ ID NO: 714, SEQ ID NO: 719, ID NO: 724, SEQ ID NO: 729, SEQ ID NO: 734, SEQ ID NO: 739, SEQ ID NO: 744, SEQ ID NO: 749, SEQ ID NO: 754, SEQ ID NO: 759, SEQ SEQ ID NO: 605, SEQ ID NO: 610, SEQ ID NO: 615, SEQ ID NO: 620, SEQ ID NO: 625, SEQ ID NO: 630, SEQ ID NO: 635, SEQ ID NO: 640, SEQ ID NO: 645, SEQ ID NO: 650, SEQ ID NO: 655, SEQ ID NO: 660, SEQ ID NO: 665, SEQ ID NO: 670, SEQ ID NO: 675, SEQ ID NO: 680, SEQ ID NO: 685, SEQ ID NO: 690, SEQ ID NO: 695, SEQ ID NO: 700, SEQ ID NO: 705, SEQ ID NO: 710, SEQ ID NO: 715, SEQ ID 720, SEQ ID NO: 725, SEQ ID NO: 730, SEQ ID NO: 735, SEQ ID NO: 740, SEQ ID NO: 745, SEQ ID NO: 750, SEQ ID NO: 755, SEQ ID NO: 760, SEQ SEQ ID NO: 606, SEQ ID NO: 611, SEQ ID NO: 616, SEQ ID NO: 621, SEQ ID NO: 626, SEQ ID NO: 631, SEQ ID NO: 636, SEQ ID NO: 641, SEQ ID NO: 646, SEQ ID NO: 651, SEQ ID NO: 656, SEQ ID NO: 661, SEQ ID NO: 666, SEQ ID NO: 671, SEQ ID NO: 676, SEQ ID NO: 681, SEQ ID NO: 686, SEQ ID NO: 691, SEQ ID NO: 696, SEQ ID NO: 701, SEQ ID NO: 706, SEQ ID NO: 711, SEQ ID NO: 716, ID NO: 721, SEQ ID NO: 726, SEQ ID NO: 731, SEQ ID NO: 736, SEQ ID NO: 741, SEQ ID NO: 746, SEQ ID NO: 751, SEQ ID NO: 756, SEQ ID NO: 761, SEQ Petição 870260017816, de 25 / 02 / 2026, pág. 20 / 45 / 27 ID NO: 762, SEQ ID NO: 763, SEQ IDNO ID NO: 767, SEQ ID NO: 768, SEQ IDNO ID NO: 772, SEQ ID NO: 773, SEQ IDNO ID NO: 777, SEQ ID NO: 778, SEQ IDNO ID NO: 782, SEQ ID NO: 783, SEQ IDNO ID NO: 787, SEQ ID NO: 788, SEQ IDNO ID NO: 792, SEQ ID NO: 793, SEQ IDNO ID NO: 797, SEQ ID NO: 798, SEQ IDNO ID NO: 802, SEQ ID NO: 803, SEQ IDNO ID NO: 807, SEQ ID NO: 808, SEQ IDNO ID NO: 812, SEQ ID NO: 813, SEQ IDNO ID NO: 817, SEQ ID NO: 818, SEQ IDNO ID NO: 822, SEQ ID NO: 823, SEQ IDNO ID NO: 827, SEQ ID NO: 828, SEQ IDNO ID NO: 832, SEQ ID NO: 833, SEQ IDNO ID NO: 837, SEQ ID NO: 838, SEQ IDNO ID NO: 842, SEQ ID NO: 843, SEQ IDNO ID NO: 847, SEQ ID NO: 848, SEQ IDNO ID NO: 852, SEQ ID NO: 853, SEQ IDNO ID NO: 857, SEQ ID NO: 858, SEQ IDNO ID NO: 862, SEQ ID NO: 863, SEQ IDNO ID NO: 867, SEQ ID NO: 868, SEQ IDNO ID NO: 872, SEQ ID NO: 873, SEQ IDNO ID NO: 877, SEQ ID NO: 878, SEQ IDNO ID NO: 882, SEQ ID NO: 883, SEQ IDNO ID NO: 887, SEQ ID NO: 888, SEQ IDNO ID NO: 892, SEQ ID NO: 893, SEQ IDNO ID NO: 897, SEQ ID NO: 898, SEQ IDNO ID NO: 902, SEQ ID NO: 903, SEQ IDNO ID NO: 907, SEQ ID NO: 908, SEQ IDNO ID NO: 912, SEQ ID NO: 913, SEQ IDNO ID NO: 917, SEQ ID NO: 918, SEQ IDNO , SEQ ID NO: 765, SEQ ID NO: 766, SEQ , SEQ ID NO: 770, SEQ ID NO: 771, SEQ , SEQ ID NO: 775, SEQ ID NO: 776, SEQ , SEQ ID NO: 780, SEQ ID NO: 781, SEQ , SEQ ID NO: 785, SEQ ID NO: 786, SEQ , SEQ ID NO: 790, SEQ ID NO: 791, SEQ , SEQ ID NO: 795, SEQ ID NO: 796, SEQ , SEQ ID NO: 800, SEQ ID NO: 801, SEQ , SEQ ID NO: 805, SEQ ID NO: 806, SEQ , SEQ ID NO: 810, SEQ ID NO: 811, SEQ , SEQ ID NO: 815, SEQ ID NO: 816, SEQ , SEQ ID NO: 820, SEQ ID NO: 821, SEQ , SEQ ID NO: 825, SEQ ID NO: 826, SEQ , SEQ ID NO: 830, SEQ ID NO: 831, SEQ , SEQ ID NO: 835, SEQ ID NO: 836, SEQ , SEQ ID NO: 840, SEQ ID NO: 841, SEQ , SEQ ID NO: 845, SEQ ID NO: 846, SEQ , SEQ ID NO: 850, SEQ ID NO: 851, SEQ , SEQ ID NO: 855, SEQ ID NO: 856, SEQ , SEQ ID NO: 860, SEQ ID NO: 861, SEQ , SEQ ID NO: 865, SEQ ID NO: 866, SEQ , SEQ ID NO: 870, SEQ ID NO: 871, SEQ , SEQ ID NO: 875, SEQ ID NO: 876, SEQ , SEQ ID NO: 880, SEQ ID NO: 881, SEQ , SEQ ID NO: 885, SEQ ID NO: 886, SEQ ,SEQ ID NO: 890, SEQ ID NO: 891, SEQ , SEQ ID NO: 895, SEQ ID NO: 896, SEQ , SEQ ID NO: 900, SEQ ID NO: 901, SEQ , SEQ ID NO: 905, SEQ ID NO: 906, SEQ , SEQ ID NO: 910, SEQ ID NO: 911, SEQ , SEQ ID NO: 915, SEQ ID NO: 916, SEQ , SEQ ID NO: 920, SEQ ID NO: 921, SEQ, Petição 870260017816, de 25 / 02 / 2026, pág. 21 / 45 / 27 ID NO: 922, SEQ ID NO: 923, SEQ ID NO: 924, SEQ ID NO: 925, SEQ ID NO: 926, SEQ ID NO: 927, SEQ ID NO: 928, SEQ ID NO: 929, SEQ ID NO: 930, SEQ ID NO: 931, SEQ ID NO: 932, SEQ ID NO: 933, SEQ ID NO: 934, SEQ ID NO: 935, SEQ ID NO: 936, SEQ ID NO: 937, SEQ ID NO: 938, SEQ ID NO: 939, SEQ ID NO: 940, SEQ ID NO: 941, SEQ ID NO: 942, SEQ ID NO: 943, SEQ ID NO: 944, SEQ ID NO: 945, SEQ ID NO: 946, SEQ ID NO: 947, SEQ ID NO: 948, SEQ ID NO: 949, SEQ ID NO: 950, SEQ ID NO: 951, SEQ ID NO: 952, SEQ ID NO: 953, SEQ ID NO: 954, SEQ ID NO: 955, SEQ ID NO: 956, SEQ ID NO: 957, SEQ ID NO: 958, SEQ ID NO: 959, SEQ ID NO: 960, SEQ ID NO: 961, SEQ ID NO: 962, SEQ ID NO: 963, SEQ ID NO: 964, SEQ ID NO: 965, SEQ ID NO: 966, SEQ ID NO: 967, SEQ ID NO: 968, SEQ ID NO: 969, SEQ ID NO: 970, SEQ ID NO: 971, SEQ ID NO: 972, SEQ ID NO: 973, SEQ ID NO: 974, SEQ ID NO: 975, SEQ ID NO: 976, SEQ ID NO: 977, SEQ ID NO: 978, SEQ ID NO: 979, SEQ ID NO: 980, SEQ ID NO: 981, SEQ ID NO: 982, SEQ ID NO: 983, SEQ ID NO: 984, SEQ ID NO: 985, SEQ ID NO: 986, SEQ ID NO: 987, SEQ ID NO: 988, SEQ ID NO: 989, SEQ ID NO: 990, SEQ ID NO: 991, SEQ ID NO: 992, SEQ ID NO: 993, SEQ ID NO: 994, SEQ ID NO: 995, SEQ ID NO: 996, SEQ ID NO: 997, SEQ ID NO: 998, SEQ ID NO: 999, SEQ ID NO: 1000, SEQ ID NO: 1001, SEQ ID NO: 1002, SEQ ID NO: 1003, SEQ ID NO: 1004, SEQ ID NO: 1005, SEQ ID NO: 1006, SEQ ID NO: 1007, SEQ ID NO: 1008, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1011, SEQ ID NO: 1012, SEQ ID NO: 1013, SEQ ID NO: 1014, SEQ ID NO: 1015, SEQ ID NO: 1016, SEQ ID NO: 1017, SEQ ID NO: 1018, SEQ ID NO: 1019, SEQ ID NO: 1020, SEQ ID NO: 1021, SEQ ID NO: 1022, SEQ ID NO: 1023, SEQ ID NO: 1024, SEQ ID NO: 1025, SEQ ID NO: 1026, SEQ ID NO: 1027, SEQ ID NO: 1028, SEQ ID NO: 1029, SEQ ID NO: 1030, SEQ ID NO: 1031, SEQ ID NO: 1032, SEQ ID NO: 1033, SEQ ID NO: 1034, SEQ ID NO: 1035, SEQ ID NO: 1036, SEQ ID NO: 1037, SEQ ID NO: 1038, SEQ ID NO: 1039, SEQ ID NO: 1040, SEQ ID NO: 1041, SEQ ID NO: 1042, SEQ ID NO: 1043, SEQ ID NO: 1044, SEQ ID NO: 1045, SEQ ID NO: 1046, SEQ ID NO: 1047, SEQ ID NO: 1048, SEQ ID NO: 1049, SEQ ID NO: 1050, SEQ ID NO: 1051, SEQ ID NO: 1052, SEQ ID NO: 1053, SEQ ID NO: 1054, SEQ ID NO: 1055, SEQ ID NO: 1056, SEQ ID NO: 1057, SEQ ID NO: 1058, SEQ ID NO: 1059, SEQ ID NO: 1060, SEQ ID NO: 1061, SEQ ID NO: 1062, SEQ ID NO: 1063, SEQ ID NO: 1064, SEQ ID NO: 1065, SEQ ID NO: 1066, SEQ ID NO: 1067, SEQ ID NO: 1068, SEQ ID NO: 1069, SEQ ID NO: 1070, SEQ ID NO: 1071. Petition 870260017816, dated 25 / 02 / 2026, page 22 / 45 / 27

[0027] The present invention is characterized by the fact that the antisense oligonucleotides are synthesized with first-generation chemical modifications of the phosphorothioate type, with the substitution of oxygen atoms by sulfur, but not limited to: other first, second or third generation modifications.

[0028] The present invention is characterized by the fact that the first-generation chemical modifications of the phosphorothioate type are in the two phosphodiester bonds at the 3' and 5' ends, but not limited to: additional modifications or modifications in other positions of the ASO.

[0029] The ASO was designed from the coding sequence (CDS) of each gene, which was retrieved from the National Center for Biotechnology Information (NCBI) website (https: / / blast.ncbi.nlm.nih.gov / Blast.cgi). The design of the antisense oligodeoxyribonucleotides was performed using the OligoWalk software. The efficiency of the ASOs was assessed for the self-formation of secondary structures (hairpins), using the Mfold software (mfold.rit.albany.edu).

[0030] Specificity to the target transcript was analyzed by alignment against the corresponding genome available in the Phytozome database (https: / / phytozome.jgi.doe.gov / pz / portal.html) and NCBI. A maximum sequence homology of up to 16 nucleotides with non-target sequences was allowed to consider ASO as a potential candidate. As an experimental control, a random nonesense oligo, without complementarity to gene sequences of the target organisms, was used.

[0031] The synthesis of ASOs was carried out by the company IDT (https: / / www.idtdna.com / pages / products / functionalgenomics / antisense-oligos). Phosphorothioate-type modifications were added to ASOs at the two 3' and 5' end internucleotide bonds to increase the molecule's stability. DNA with these modifications exhibits greater nuclease resistance, lower toxicity, and increased hybridization affinities in vivo.

[0032] The selection of the sequence for the assays and nanostructuring was based on the GC content in the range of (40-60%), lower binding energy [Overall (ΔG)] and the location of the target sequence in the first exon of the DMR6 and LIN6 genes, and therefore, the Petition 870260017816, dated 25 / 02 / 2026, page 23 / 45 / 27 SEQ ID NO: 150 and SEQ ID NO: 1045, respectively, were used in in planta tests and subsequently for nanostructuring.

[0033] The present invention is characterized by further comprising nanostructured modified antisense oligonucleotides with a natural biopolymer followed by the addition of a synthetic polymer as a copolymer. More specifically, the present invention relates to the biopolymer chitosan and the copolymer polyethylene glycol.

[0034] The present invention is further related to compositions for controlling plant diseases using free or nanostructured modified antisense oligonucleotides, as described in this patent application, and an agronomically acceptable carrier. More specifically, the composition relates to the following agronomically acceptable carriers: chitosan crosslinked by ionic gelation with sodium tripolyphosphate followed by the addition of polyethylene glycol.

[0035] The carrier nanoparticles were obtained from the following steps: a. Synthesis of the antisense oligonucleotide as described in the invention; b. Solubilization of the natural biopolymer in an acidified aqueous reaction medium; c. Addition of the oligonucleotides selected in “a” to the solution obtained in “b” to a concentration of 0.1 to 10 μM; d. Addition of sodium tripolyphosphate solution to the solution obtained in “c” to perform ionic gelation; e. Maintaining the suspension obtained in “d” using magnetic stirring; and f. Addition of polyethylene glycol to the solution obtained in “e”.

[0036] The nanoparticle obtained is characterized by the fact that the natural biopolymer is selected from, but not limited to: chitosan, alginate, carrageenan, gellan gum, gelatin, casein, agarose, hydroxypropylmethylcellulose and several others. Also, but not limited to these, synthetic polymers such as polyethylene glycol (PEG), poly(acrylic acid) (PAA), poly(vinyl alcohol) (PVA), polymers containing carboxylates, among others, may be used. More specifically, the present invention relates to the biopolymer chitosan and the copolymer PEG. Petition 870260017816, dated 25 / 02 / 2026, page 24 / 45 / 27

[0037] As a form of nanostructuring, the methods that can be employed include, but are not limited to: gelation, precipitation, complex coacervation, solvent emulsification / evaporation, electrospinning, electrospraying, supercritical techniques, microfluidics, self-assembly, and complex formation with molecules and other nanomaterials. As crosslinking agents, monovalent (Na+ and K+), divalent (Ca2+, Ba2+, Mg2+) or trivalent (Fe3+ and Al3+) cations can be used, depending on the case, for anionic polymers such as alginate, pectin, carrageenan; monovalent anions (chloride and acetate), divalent anions (sulfate and citrate), polyphosphates or polyanions (sodium tripolyphosphate, sodium hexametaphosphate and tricalcium phosphate) for cationic polymers such as chitosan; other ionic crosslinking agents such as borate ions, copper ions and zinc ions.More specifically, the present invention relates to chitosan biopolymer gelled with sodium tripolyphosphate followed by the addition of PEG.

[0038] This application also describes the use of modified antisense oligonucleotides for the control of plant diseases. When ASO enters the plant cell, it forms a DNA:mRNA hybrid, recognized by the RNase H enzyme which cleaves the mRNA strand, leading to the silencing of the target susceptibility gene. Consequently, there is a reduction in disease symptoms in the plant.

[0039] Such diseases may be selected from the group, but are not limited to: late blight or blight caused by Phytophthora infestans, downy mildew caused by Hyaloperonospora arabidopsidis, bacterial spot caused by Pseudomonas syringae, fruit rot caused by Pseudomonas capsici, pith necrosis caused by Pseudomonas spp., bacterial wilt caused by Pseudomonas Ralstonia solanacearum, hollow stem or soft rot caused by Pectobacterium spp., bacterial canker caused by Clavibacter michiganensis subsp. michiganensis, bacterial speck caused by Pseudomonas syringae pv. tomato, stem canker caused by Alternaria alternata f. sp. lycopersici, white mold caused by Sclerotinia sclerotiorum, gray mold caused by Botrytis cinerea, anthracnose caused by Colletotrichum spp., fusarium wilt, caused by Fusarium oxysporum f. sp.lycopersici, black spot caused by Alternaria solani, septoria leaf spot caused by Septoria lycopersici, powdery mildew caused by Oidium neolycopersici and Oidiopsis haplophylli. Petition 870260017816, dated 25 / 02 / 2026, p. 25 / 45 / 27 root rot caused by Rhizoctonia solani, stenphylium leaf spot caused by Stemphylium solani and Stemphylium lycopersici, deer eye rot caused by Phytophthora spp., brown root rot caused by Pyrenochaeta lycopersici, target spot caused by Corynespora cassiicola, tomato spotted wilt virus caused by Orthotospovirus and golden mosaic virus caused by Begomovirus.

[0040] Preferably, the disease is bacterial spot of tomato (MBT) caused by Xanthomonas spp.

[0041] Plants that can benefit from the present invention may include, but are not limited to: beans, rice, soybeans, coffee, barley, wheat, corn, tubers such as potatoes, cassava, sweet potatoes, vegetables such as lettuce, broccoli, garlic, onions, kale, cauliflower, cabbage, Brussels sprouts, fruit trees such as melon, papaya, mango, peach, plum, pear, apple, preferably tomato (Solanum lycopersicum).

[0042] The oligonucleotides, nanoparticles and compositions of the invention can be applied to plants in liquid form, by foliar application, in the soil, in water or by infiltration, but not limited to: emulsion, gel, semi-solid powder, powder, granules, pellets and other compatible formulations.

[0043] The present invention is illustrated in the following examples, which are not intended to limit the invention in any way. The examples will refer to the figures described above. Examples of embodiments of the invention 1. Selection, modification and synthesis of antisense oligodeoxynucleotides (ASOs)

[0044] Based on previous gene expression experiments conducted by our group, the Downy Mildew Resistance 6 (DMR6) and Invertase 6 (LIN6) genes were selected for evaluation of gene silencing mediated by antisense oligodeoxynucleotides (ASO). The coding sequence (CDS) of each gene was retrieved from the National Center for Biotechnology Information (NCBI) website (https: / / blast.ncbi.nlm.nih.gov / Blast.cgi). The design of the oligodeoxyribonucleotides Petition 870260017816, dated 25 / 02 / 2026, p. 26 / 45 / 27. Antisense analysis was performed using OligoWalk and Sfold software (https: / / sfold.wadsworth.org / cgi-bin / index.pl). Only ASOs present in both software programs were selected. The efficiency of the ASOs was then measured regarding the self-formation of secondary structures (hairpins) using Mfold software (mfold.rit.albany.edu). Specificity to the target transcript was analyzed through alignment against the corresponding genome available in the Phytozome database (https: / / phytozome.jgi.doe.gov / pz / portal.html) and NCBI. A maximum sequence homology of up to 16 nucleotides with non-target sequences was allowed to consider the ASO as a potential candidate. Priority was also given to ASOs that presented the target sequence in the first exon of the gene.

[0045] As an experimental control, a random nonesense oligo, without complementarity to gene sequences of the target organisms, was used. The synthesis of the ASOs was carried out by the company IDT (https: / / www.idtdna.com / pages / products / functionalgenomics / antisenseoligos). Phosphorothioate-type modifications were added to the ASOs at the two internucleotide bonds of the 3' and 5' ends to increase the stability of the molecule. The DNA with these modifications exhibits greater nuclease resistance, lower toxicity, and increased hybridization affinities in vivo. 2. Treatment of plants with ASO and inoculation with Xanthomonas euvesicatoria pv. perforans

[0046] A total of 3 tomato plants were used for each of the treatments (ASODMR6, ASO-LIN6, Random, and water). The treatments consisted of infiltrating the random ASOs (control), ASO-DMR6 (SEQ ID NO: 150), and ASO-LIN6 (SEQ ID NO: 1045) into tomato leaves. All ASOs were infiltrated at 4 different points on the leaves using a needleless syringe at a concentration of 10 μM. 24 h after ASO infiltration, the plants were inoculated with Xanthomonas euvesicatoria pv. perforans (Xep) (OD600 = 0.3) by spraying and immediately placed in humid chamber conditions for 48 h. All experiments were conducted in a greenhouse. Each treatment was represented by three biological triplicates, and in each replicate, 3 leaves were analyzed, totaling 9 samples / treatment. Initially, three distinct experiments were conducted using ASO-DMR6 and ASO-LIN6 at a concentration of 10 μM. Petition 870260017816, dated 25 / 02 / 2026, page 27 / 45 / 27

[0047] In subsequent experiments, ASOs were used at final concentrations of 1 μM and 0.1 μM. In some experiments, treatment with the chemical compound acibenzolar-S-methyl, an analogue of salicylic acid (ASA), considered a plant defense inducer and used for the prophylactic control of MBT, was added for comparison. Symptoms were evaluated 15 to 20 days after bacterial inoculation. Lesions were photographed and analyzed to compare symptoms between treatments. The severity of symptoms was quantified using ImageJ or Quant software (Liberato, 2003, Development and evaluation of the QUANT software for quantification of plant diseases by image analysis. 2003. 112 p. Thesis (Doctorate in Phytopathology) - Federal University of Viçosa, Viçosa). The data obtained were then used to calculate the percentage of leaf area damaged. 3. Development of a nanoformulation based on antisense oligonucleotides

[0048] Aiming to increase the potential for silencing target genes, DMR6 and LIN6 ASOs were nanoencapsulated. For the delivery of antisense oligonucleotides (ASOs), a strategy based on ionic gelation of chitosan with sodium tripolyphosphate followed by functionalization of the formed structures with polyethylene glycol (PEG) was used. In this sense, chitosan (CH) and sodium tripolyphosphate (TPP) solutions were prepared, and ASOs were added to the CH solution to the defined final concentration, followed by dropwise addition of the TPP solution. The final suspension was then maintained under magnetic stirring. Subsequently, a PEG solution was added to this solution, and the nanostructure suspension was refrigerated until the characterization steps (dynamic light scattering and Zeta potential) or activity tests were performed. Control structures without ASOs were also produced as controls (empty nanoparticles).

[0049] For the nanoparticles containing ASO-DMR6, an average hydrodynamic diameter (Z-average) of 736.9 ± 54.5 nm, a polydispersity index (PdI) of 0.937 ± 0.110, and a Zeta potential of 28.10 ± 3.97 mV were obtained. Furthermore, a range of diameter variation was obtained for the nanostructures detected based on the hydrodynamic diameter distribution curves, ranging from 32.7 to 955.4 nm. For the nanoparticles containing ASO-LIN6, an average hydrodynamic diameter was obtained. Petition 870260017816, dated 25 / 02 / 2026, page 28 / 45 / 27 (Zaverage) of 638.6 ± 106.3 nm, polydispersity index (Pdl) of 0.999 ± 0.002 and Zeta potential of 25.30 ± 1.57 mV. In addition, a range of diameter variation of the detected nanostructures was obtained based on the hydrodynamic diameter distribution curves, numbering from 21.0 to 396.1 nm.

[0050] As a control, for the empty (white) nanoparticles without ASO, the average hydrodynamic diameter (Z-average) of 612.0 ± 17.3 nm, polydispersity index (Pdl) of 0.962 ± 0.066, and Zeta potential of 25.60 ± 2.38 mV were obtained. In addition, the diameter variation range of the detected nanostructures was obtained based on the hydrodynamic diameter distribution curves, ranging from 28.2 to 615.1 nm.

[0051] The application of the nanoformulations was carried out on tomato plants as described in section 1 for free ASOs. However, concentrations of 1 μM, 0.5 μM and 0.1 μM were tested. The analysis of symptoms was carried out as described for free (non-nanostructured) ASOs. 4. Inoculation of free ASOs in tomato plants and evaluation of symptoms.

[0052] Initially, 3 experiments were carried out at different times using ASOs DMR6 and LIN6 at 10 μM free for tomato. Symptoms were evaluated at 12 and 15 days after inoculation (dai) and the results revealed that ASO-DMR6 and ASO-LIN6 were effective in protecting the plant against infection by X. euvesicatoria pv. perforans up to 15 dai (Figure 1 and Figure 2).

[0053] The onset of symptoms occurred 12 days after inoculation (dai) with Xep. At 15 dai, plants treated with Random (10 μM) showed a more affected phenotype when compared to plants treated with the ASO DMR6 and LIN6. Thus, the results showed that the application of ASOs for the DMR6 and LIN6 genes at a concentration of 10 μM was able to silence the DMR6 and LIN6 genes in planta. These results are valuable and can be used as a strategy for controlling this pathogen.

[0054] Subsequently, a fourth experiment was carried out with the aim of confirming the results obtained in the previous experiments and testing lower concentrations of ASO. Tomato plants were infiltrated with ASO-DMR6 [1 and 10 μM], ASO-Random [1 and 10 Petition 870260017816, dated 02 / 25 / 2026, page 29 / 45 / 27 μM], ASO-LIN6 [1 μM]. As a control treatment, plants were also sprayed with the chemical compound acibenzolar-S-methyl (ASM), an analogue of salicylic acid (AAS), considered a plant defense inducer, used for the prophylactic control of MBT. Control conditions of water infiltration and a control (no treatment) were also included. 24 h after the application of the treatments, a solution of Xep was sprayed on all plants. The evaluation of MBT symptoms was performed 20 days after inoculation (dai).

[0055] The quantification of the symptomatic area was performed using ImageJ software, and the results showed that plants treated with ASO-DMR6 [10 μM] were able to delay symptoms, while in plants treated with ASO-Random, progressive symptoms were observed, suggesting that ASO-DMR6 is efficient in controlling the disease (Figure 3). At a concentration of 1 μM, ASO-LIN6 proved to be efficient in reducing MBT symptoms when compared to the control condition (Figure 4). Although ASO-DMR6 [1 μM] did not result in a decrease in symptoms with statistical validation, it is possible to observe that the plants presented a healthier appearance when compared to plants treated with ASO-Random [1 μM] (Figure 4). These observations strongly suggest that these ASOs have a high potential for generating a product that can contribute to the control of Xanthomonas in tomato plants. 5. Application of nanostructured ASOs in tomato plants and evaluation of symptoms.

[0056] The application of nanostructured ASOs was carried out on tomato plants as described above for free ASOs, at different concentrations, 1 μM and 0.5 μM, in addition to free ASO at 10 μM and / or 1 μM. The analysis of foliar symptoms (Figure 5 and Figure 6) indicated the effectiveness of treatments with nanoencapsulated ASOs at concentrations up to 20 times lower than those of free ASO.

[0057] In subsequent experiments, tomato plants were infiltrated with ASODMR6 [1 and 0.1 μM], ASO-Random [1 and 0.1 μM], Nano-DMR6 [1 and 0.1 μM], Nano-LIN6 [1 and 0.1 μM], and NanoVazia. The treatments were compared with the chemical compound acibenzolar-S-methyl (AAS), in addition to the control condition (Water) (Figure 7, Figure 8 and Figure 9). Petition 870260017816, dated 25 / 02 / 2026, page 30 / 45 / 27 9) 24 h after ASO infiltration, the plants were inoculated with Xep. The results showed that plants treated with ASO-DMR6 [1 μM] exhibited healthier phenotypes when compared to plants treated with ASO-Random [1 μM] (Figure 7).

[0058] When plants treated with nanoencapsulated ASOs were compared with plants treated with Nano-vazia, it was observed that plants treated with nanoencapsulated ASOs showed a significant reduction in symptoms. 6. Silencing the DMR6 gene

[0059] For gene expression assessment, tomato plants were infiltrated with approximately 300 μL of Nano-DMR6 [1 μM] or Nano-empty or treated with H2O (control plants). Leaves were collected 24 h after infiltration. RNA extraction was performed using the Trizol method (Invitrogen) and cDNA was synthesized using a GoScript™ Reverse Transcriptase kit (Promega, Madison, WI, USA). RTqPCR was performed using GoTaq® qPCR Master Mix (Promega, Madison, WI, USA). Subsequently, relative expression was analyzed using the Methylated histone binding (PHD) and Small nuclear ribonucleoprotein family protein (LSM7) genes as normalizing genes, using the ΔΔCT calculation.

[0060] When plants inoculated with Nano-DMR6 were compared to plants treated with H2O or Nano-empty, the results showed that the DMR6 gene was downregulated after inoculation in plants treated with Nano-DMR6 (Figure 10). The results obtained in this study indicate that the application of DMR6 ASO appears to be efficient in silencing, with a lower level of gene expression observed when compared to control conditions. Furthermore, the commitment of orthologs of the same S gene in different plant species may potentially result in resistance to different pathogens. Petition 870260017816, dated 25 / 02 / 2026, page 31 / 45

Claims

1 / 10 CLAIMS 1. MODIFIED ANTISENSE OLIGONUCLEOTIDE (ASOs), characterized by comprising at least 90%, more specifically 95%, more specifically 98%, more specifically 99% sequence similarity with any of the selected sequences from the group: SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9, SEQ ID NO 10, SEQ ID NO 11, SEQ ID NO 12, SEQ ID NO 13, SEQ ID NO 14, SEQ ID NO 15, SEQ ID NO 16, SEQ ID NO 17, SEQ ID NO 18, SEQ ID NO 19, SEQ ID NO 20, SEQ ID NO 21, SEQ ID NO 22, SEQ ID NO 23, SEQ ID NO 24, SEQ ID NO 25, SEQ ID NO 26, SEQ ID NO 27, SEQ ID NO 28, SEQ ID NO 29, SEQ ID NO 30, SEQ ID NO 31, SEQ ID NO 32, SEQ ID NO 33, SEQ ID NO 34, SEQ ID NO 35, SEQ ID NO 36, SEQ ID NO 37, SEQ ID NO 38, SEQ ID NO 39, SEQ ID NO 40, SEQ ID NO 41, SEQ ID NO 42, SEQ ID NO 43, SEQ ID NO 44, SEQ ID NO 45, SEQ ID NO 46, SEQ ID NO 47, SEQ ID NO 48, SEQ ID NO 49, SEQ ID NO 50, SEQ ID NO 51, SEQ ID NO 52, SEQ ID NO 53, SEQ ID NO 54,SEQ ID NO 55, SEQ ID NO 56, SEQ ID NO 57, SEQ ID NO 58, SEQ ID NO 59, SEQ ID NO 60, SEQ ID NO 61, SEQ ID NO 62, SEQ ID NO 63, SEQ ID NO 64, SEQ ID NO 65, SEQ ID NO 66, SEQ ID NO 67, SEQ ID NO 68, SEQ ID NO 69, SEQ ID NO 70, SEQ ID NO 71, SEQ ID NO 72, SEQ ID NO 73, SEQ ID NO 74, SEQ ID NO 75, SEQ ID NO 76, SEQ ID NO 77, SEQ ID NO 78, SEQ ID NO 79, SEQ ID NO 80, SEQ ID NO 81, SEQ ID NO 82, SEQ ID NO 83, SEQ ID NO 84, SEQ ID NO 85, SEQ ID NO 86, SEQ ID NO 87, SEQ ID NO 88, SEQ ID NO 89, SEQ ID NO 90, SEQ ID NO 91, SEQ ID NO 92, SEQ ID NO 93, SEQ ID NO 94, SEQ ID NO 95, SEQ ID NO 96, SEQ ID NO 97, SEQ ID NO 98, SEQ ID NO 99, SEQ ID NO 100, SEQ ID NO 101, SEQ ID NO 102, SEQ ID NO 103, SEQ ID NO 104, SEQ ID NO 105, SEQ ID NO 106, SEQ ID NO 107, SEQ ID NO 108, SEQ ID NO 109, SEQ ID NO 110, SEQ ID NO 111, SEQ ID NO 112, SEQ ID NO 113, SEQ ID NO 114, SEQ ID NO 115, SEQ ID NO 116, SEQ ID NO 117, SEQ ID NO 118, SEQ ID NO 119, SEQ ID NO 120, SEQ ID NO 121, SEQ ID NO 122, SEQ ID NO 123,SEQ ID NO 124, SEQ ID NO 125, SEQ ID NO 126, SEQ ID NO 127, SEQ ID NO 128, SEQ ID NO 129, Petição 870250039936, de 15 / 05 / 2025, pág. 36 / 65 2 / 10 SEQ ID NO 130, SEQ ID NO 131, SEQ ID NO 132, SEQ ID NO 133, SEQ ID NO 134, SEQ ID NO 135, SEQ ID NO 136, SEQ ID NO 137, SEQ ID NO 138, SEQ ID NO 139, SEQ ID NO 140, SEQ ID NO 141, SEQ ID NO 142, SEQ ID NO 143, SEQ ID NO 144, SEQ ID NO 145, SEQ ID NO 146, SEQ ID NO 147, SEQ ID NO 148, SEQ ID NO 149, SEQ ID NO 150, SEQ ID NO 151, SEQ ID NO 152, SEQ ID NO 153, SEQ ID NO 154, SEQ ID NO 155, SEQ ID NO 156, SEQ ID NO 157, SEQ ID NO 158, SEQ ID NO 159, SEQ ID NO 160, SEQ ID NO 161, SEQ ID NO 162, SEQ ID NO 163, SEQ ID NO 164, SEQ ID NO 165, SEQ ID NO 166, SEQ ID NO 167, SEQ ID NO 168, SEQ ID NO 169, SEQ ID NO 170, SEQ ID NO 171, SEQ ID NO 172, SEQ ID NO 173, SEQ ID NO 174, SEQ ID NO 175, SEQ ID NO 176, SEQ ID NO 177, SEQ ID NO 178, SEQ ID NO 179, SEQ ID NO 180, SEQ ID NO 181, SEQ ID NO 182, SEQ ID NO 183, SEQ ID NO 184, SEQ ID NO 185, SEQ ID NO 186,SEQ ID NO 187, SEQ ID NO 188, SEQ ID NO 189, SEQ ID NO 190, SEQ ID NO 191, SEQ ID NO 192, SEQ ID NO 193, SEQ ID NO 194, SEQ ID NO 195, SEQ ID NO 196, SEQ ID NO 197, SEQ ID NO 198, SEQ ID NO 199, SEQ ID NO 200, SEQ ID NO 201, SEQ ID NO 202, SEQ ID NO 203, SEQ ID NO 204, SEQ ID NO 205, SEQ ID NO 206, SEQ ID NO 207, SEQ ID NO 208, SEQ ID NO 209, SEQ ID NO 210, SEQ ID NO 211, SEQ ID NO 212, SEQ ID NO 213, SEQ ID NO 214, SEQ ID NO 215, SEQ ID NO 216, SEQ ID NO 217, SEQ ID NO 218, SEQ ID NO 219, SEQ ID NO 220, SEQ ID NO 221, SEQ ID NO 222, SEQ ID NO 223, SEQ ID NO 224, SEQ ID NO 225, SEQ ID NO 226, SEQ ID NO 227, SEQ ID NO 228, SEQ ID NO 229, SEQ ID NO 230, SEQ ID NO 231, SEQ ID NO 232, SEQ ID NO 233, SEQ ID NO 234, SEQ ID NO 235, SEQ ID NO 236, SEQ ID NO 237, SEQ ID NO 238, SEQ ID NO 239, SEQ ID NO 240, SEQ ID NO 241, SEQ ID NO 242, SEQ ID NO 243, SEQ ID NO 244, SEQ ID NO 245, SEQ ID NO 246, SEQ ID NO 247, SEQ ID NO 248, SEQ ID NO 249, SEQ ID NO 250, SEQ ID NO 251, SEQ ID NO 252,SEQ ID NO 253, SEQ ID NO 254, SEQ ID NO 255, SEQ ID NO 256, SEQ ID NO 257, SEQ ID NO 258, SEQ ID NO 259, SEQ ID NO 260, SEQ ID NO 261, SEQ ID NO 262, SEQ ID NO 263, SEQ ID NO 264, SEQ ID NO 265, SEQ ID NO 266, SEQ ID NO 267, SEQ ID NO 268, SEQ ID NO 269, SEQ ID NO 270, SEQ ID NO 271, SEQ ID NO 272, SEQ ID NO 273, SEQ ID NO 274, SEQ ID NO 275, SEQ ID NO 276, SEQ Petição 870250039936, de 15 / 05 / 2025, pág. 37 / 65 3 / 10 ID NO 277, SEQ ID NO 278, SEQ ID NO 279, SEQ ID NO 280, SEQ ID NO 281, SEQ ID NO 282, SEQ ID NO 283, SEQ ID NO 284, SEQ ID NO 285, SEQ ID NO 286, SEQ ID NO 287, SEQ ID NO 288, SEQ ID NO 289, SEQ ID NO 290, SEQ ID NO 291, SEQ ID NO 292, SEQ ID NO 293, SEQ ID NO 294, SEQ ID NO 295, SEQ ID NO 296, SEQ ID NO 297, SEQ ID NO 298, SEQ ID NO 299, SEQ ID NO 300, SEQ ID NO 301, SEQ ID NO 302, SEQ ID NO 303, SEQ ID NO 304, SEQ ID NO 305, SEQ ID NO 306, SEQ ID NO 307, SEQ ID NO 308, SEQ ID NO 309, SEQ ID NO 310, SEQ ID NO 311, SEQ ID NO 312, SEQ ID NO 313, SEQ ID NO 314, SEQ ID NO 315,SEQ ID NO 316, SEQ ID NO 317, SEQ ID NO 318, SEQ ID NO 319, SEQ ID NO 320, SEQ ID NO 321, SEQ ID NO 322, SEQ ID NO 323, SEQ ID NO 324, SEQ ID NO 325, SEQ ID NO 326, SEQ ID NO 327, SEQ ID NO 328, SEQ ID NO 329, SEQ ID NO 330, SEQ ID NO 331, SEQ ID NO 332, SEQ ID NO 333, SEQ ID NO 334, SEQ ID NO 335, SEQ ID NO 336, SEQ ID NO 337, SEQ ID NO 338, SEQ ID NO 339, SEQ ID NO 340, SEQ ID NO 341, SEQ ID NO 342, SEQ ID NO 343, SEQ ID NO 344, SEQ ID NO 345, SEQ ID NO 346, SEQ ID NO 347, SEQ ID NO 348, SEQ ID NO 349, SEQ ID NO 350, SEQ ID NO 351, SEQ ID NO 352, SEQ ID NO 353, SEQ ID NO 354, SEQ ID NO 355, SEQ ID NO 356, SEQ ID NO 357, SEQ ID NO 358, SEQ ID NO 359, SEQ ID NO 360, SEQ ID NO 361, SEQ ID NO 362, SEQ ID NO 363, SEQ ID NO 364, SEQ ID NO 365, SEQ ID NO 366, SEQ ID NO 367, SEQ ID NO 368, SEQ ID NO 369, SEQ ID NO 370, SEQ ID NO 371, SEQ ID NO 372, SEQ ID NO 373, SEQ ID NO 374, SEQ ID NO 375, SEQ ID NO 376, SEQ ID NO 377, SEQ ID NO 378, SEQ ID NO 379, SEQ ID NO 380, SEQ ID NO 381,SEQ ID NO 382, SEQ ID NO 383, SEQ ID NO 384, SEQ ID NO 385, SEQ ID NO 386, SEQ ID NO 387, SEQ ID NO 388, SEQ ID NO 389, SEQ ID NO 390, SEQ ID NO 391, SEQ ID NO 392, SEQ ID NO 393, SEQ ID NO 394, SEQ ID NO 395, SEQ ID NO 396, SEQ ID NO 397, SEQ ID NO 398, SEQ ID NO 399, SEQ ID NO 400, SEQ ID NO 401, SEQ ID NO 402, SEQ ID NO 403, SEQ ID NO 404, SEQ ID NO 405, SEQ ID NO 406, SEQ ID NO 407, SEQ ID NO 408, SEQ ID NO 409, SEQ ID NO 410, SEQ ID NO 411, SEQ ID NO 412, SEQ ID NO 413, SEQ ID NO 414, SEQ ID NO 415, SEQ ID NO 416, SEQ ID NO 417, SEQ ID NO 418, SEQ ID NO 419, SEQ ID NO 420, SEQ ID NO 421, SEQ ID NO 422, SEQ ID NO 423, SEQ ID Petição 870250039936, de 15 / 05 / 2025, pág. 38 / 65 4 / 10 NO 424, SEQ ID NO 425, SEQ ID NO 426, SEQ ID NO 427, SEQ ID NO 428, SEQ ID NO 429, SEQ ID NO 430, SEQ ID NO 431, SEQ ID NO 432, SEQ ID NO 433, SEQ ID NO 434, SEQ ID NO 435, SEQ ID NO 436, SEQ ID NO 437, SEQ ID NO 438, SEQ ID NO 439, SEQ ID NO 440, SEQ ID NO 441, SEQ ID NO 442, SEQ ID NO 443, SEQ ID NO 444,SEQ ID NO 445, SEQ ID NO 446, SEQ ID NO 447, SEQ ID NO 448, SEQ ID NO 449, SEQ ID NO 450, SEQ ID NO 451, SEQ ID NO 452, SEQ ID NO 453, SEQ ID NO 454, SEQ ID NO 455, SEQ ID NO 456, SEQ ID NO 457, SEQ ID NO 458, SEQ ID NO 459, SEQ ID NO 460, SEQ ID NO 461, SEQ ID NO 462, SEQ ID NO 463, SEQ ID NO 464, SEQ ID NO 465, SEQ ID NO 466, SEQ ID NO 467, SEQ ID NO 468, SEQ ID NO 469, SEQ ID NO 470, SEQ ID NO 471, SEQ ID NO 472, SEQ ID NO 473, SEQ ID NO 474, SEQ ID NO 475, SEQ ID NO 476, SEQ ID NO 477, SEQ ID NO 478, SEQ ID NO 479, SEQ ID NO 480, SEQ ID NO 481, SEQ ID NO 482, SEQ ID NO 483, SEQ ID NO 484, SEQ ID NO 485, SEQ ID NO 486, SEQ ID NO 487, SEQ ID NO 488, SEQ ID NO 489, SEQ ID NO 490, SEQ ID NO 491, SEQ ID NO 492, SEQ ID NO 493, SEQ ID NO 494, SEQ ID NO 495, SEQ ID NO 496, SEQ ID NO 497, SEQ ID NO 498, SEQ ID NO 499, SEQ ID NO 500, SEQ ID NO 501, SEQ ID NO 502, SEQ ID NO 503, SEQ ID NO 504, SEQ ID NO 505, SEQ ID NO 506, SEQ ID NO 507, SEQ ID NO 508, SEQ ID NO 509, SEQ ID NO 510,SEQ ID NO 511, SEQ ID NO 512, SEQ ID NO 513, SEQ ID NO 514, SEQ ID NO 515, SEQ ID NO 516, SEQ ID NO 517, SEQ ID NO 518, SEQ ID NO 519, SEQ ID NO 520, SEQ ID NO 521, SEQ ID NO 522, SEQ ID NO 523, SEQ ID NO 524, SEQ ID NO 525, SEQ ID NO 526, SEQ ID NO 527, SEQ ID NO 528, SEQ ID NO 529, SEQ ID NO 530, SEQ ID NO 531, SEQ ID NO 532, SEQ ID NO 533, SEQ ID NO 534, SEQ ID NO 535, SEQ ID NO 536, SEQ ID NO 537, SEQ ID NO 538, SEQ ID NO 539, SEQ ID NO 540, SEQ ID NO 541, SEQ ID NO 542, SEQ ID NO 543, SEQ ID NO 544, SEQ ID NO 545, SEQ ID NO 546, SEQ ID NO 547, SEQ ID NO 548, SEQ ID NO 549, SEQ ID NO 550, SEQ ID NO 551, SEQ ID NO 552, SEQ ID NO 553, SEQ ID NO 554, SEQ ID NO 555, SEQ ID NO 556, SEQ ID NO 557, SEQ ID NO 558, SEQ ID NO 559, SEQ ID NO 560, SEQ ID NO 561, SEQ ID NO 562, SEQ ID NO 563, SEQ ID NO 564, SEQ ID NO 565, SEQ ID NO 566, SEQ ID NO 567, SEQ ID NO 568, SEQ ID NO 569, SEQ ID NO 570, SEQ ID NO Petição 870250039936, de 15 / 05 / 2025, pág. 39 / 65 5 / 10 571, SEQ ID NO 572, SEQ ID NO 573,SEQ ID NO 574, SEQ ID NO 575, SEQ ID NO 576, SEQ ID NO 577, SEQ ID NO 578, SEQ ID NO 579, SEQ ID NO 580, SEQ ID NO 581, SEQ ID NO 582, SEQ ID NO 583, SEQ ID NO 584, SEQ ID NO 585, SEQ ID NO 586, SEQ ID NO 587, SEQ ID NO 588, SEQ ID NO 589, SEQ ID NO 590, SEQ ID NO 591, SEQ ID NO 592, SEQ ID NO 593, SEQ ID NO 594, SEQ ID NO 595, SEQ ID NO 596, SEQ ID NO 597, SEQ ID NO 598, SEQ ID NO 599, SEQ ID NO 600, SEQ ID NO 601, SEQ ID NO 602, SEQ ID NO 603, SEQ ID NO 604, SEQ ID NO 605, SEQ ID NO 606, SEQ ID NO 607, SEQ ID NO 608, SEQ ID NO 609, SEQ ID NO 610, SEQ ID NO 611, SEQ ID NO 612, SEQ ID NO 613, SEQ ID NO 614, SEQ ID NO 615, SEQ ID NO 616, SEQ ID NO 617, SEQ ID NO 618, SEQ ID NO 619, SEQ ID NO 620, SEQ ID NO 621, SEQ ID NO 622, SEQ ID NO 623, SEQ ID NO 624, SEQ ID NO 625, SEQ ID NO 626, SEQ ID NO 627, SEQ ID NO 628, SEQ ID NO 629, SEQ ID NO 630, SEQ ID NO 631, SEQ ID NO 632, SEQ ID NO 633, SEQ ID NO 634, SEQ ID NO 635, SEQ ID NO 636, SEQ ID NO 637, SEQ ID NO 638, SEQ ID NO 639,SEQ ID NO 640, SEQ ID NO 641, SEQ ID NO 642, SEQ ID NO 643, SEQ ID NO 644, SEQ ID NO 645, SEQ ID NO 646, SEQ ID NO 647, SEQ ID NO 648, SEQ ID NO 649, SEQ ID NO 650, SEQ ID NO 651, SEQ ID NO 652, SEQ ID NO 653, SEQ ID NO 654, SEQ ID NO 655, SEQ ID NO 656, SEQ ID NO 657, SEQ ID NO 658, SEQ ID NO 659, SEQ ID NO 660, SEQ ID NO 661, SEQ ID NO 662, SEQ ID NO 663, SEQ ID NO 664, SEQ ID NO 665, SEQ ID NO 666, SEQ ID NO 667, SEQ ID NO 668, SEQ ID NO 669, SEQ ID NO 670, SEQ ID NO 671, SEQ ID NO 672, SEQ ID NO 673, SEQ ID NO 674, SEQ ID NO 675, SEQ ID NO 676, SEQ ID NO 677, SEQ ID NO 678, SEQ ID NO 679, SEQ ID NO 680, SEQ ID NO 681, SEQ ID NO 682, SEQ ID NO 683, SEQ ID NO 684, SEQ ID NO 685, SEQ ID NO 686, SEQ ID NO 687, SEQ ID NO 688, SEQ ID NO 689, SEQ ID NO 690, SEQ ID NO 691, SEQ ID NO 692, SEQ ID NO 693, SEQ ID NO 694, SEQ ID NO 695, SEQ ID NO 696, SEQ ID NO 697, SEQ ID NO 698, SEQ ID NO 699, SEQ ID NO 700, SEQ ID NO 701, SEQ ID NO 702, SEQ ID NO 703, SEQ ID NO 704, SEQ ID NO 705,SEQ ID NO 706, SEQ ID NO 707, SEQ ID NO 708, SEQ ID NO 709, SEQ ID NO 710, SEQ ID NO 711, SEQ ID NO 712, SEQ ID NO 713, SEQ ID NO 714, SEQ ID NO 715, SEQ ID NO 716, SEQ ID NO 717, SEQ ID NO 718, Petição 870250039936, de 15 / 05 / 2025, pág. 40 / 65 6 / 10 SEQ ID NO 719, SEQ ID 720, SEQ ID NO 721, SEQ ID NO 722, SEQ ID NO 723, SEQ ID NO 724, SEQ ID NO 725, SEQ ID NO 726, SEQ ID NO 727, SEQ ID NO 728, SEQ ID NO 729, SEQ ID NO 730, SEQ ID NO 731, SEQ ID NO 732, SEQ ID NO 733, SEQ ID NO 734, SEQ ID NO 735, SEQ ID NO 736, SEQ ID NO 737, SEQ ID NO 738, SEQ ID NO 739, SEQ ID NO 740, SEQ ID NO 741, SEQ ID NO 742, SEQ ID NO 743, SEQ ID NO 744, SEQ ID NO 745, SEQ ID NO 746, SEQ ID NO 747, SEQ ID NO 748, SEQ ID NO 749, SEQ ID NO 750, SEQ ID NO 751, SEQ ID NO 752, SEQ ID NO 753, SEQ ID NO 754, SEQ ID NO 755, SEQ ID NO 756, SEQ ID NO 757, SEQ ID NO 758, SEQ ID NO 759, SEQ ID NO 760, SEQ ID NO 761, SEQ ID NO 762, SEQ ID NO 763, SEQ ID NO 764, SEQ ID NO 765, SEQ ID NO 766, SEQ ID NO 767, SEQ ID NO 768,SEQ ID NO 769, SEQ ID NO 770, SEQ ID NO 771, SEQ ID NO 772, SEQ ID NO 773, SEQ ID NO 774, SEQ ID NO 775, SEQ ID NO 776, SEQ ID NO 777, SEQ ID NO 778, SEQ ID NO 779, SEQ ID NO 780, SEQ ID NO 781, SEQ ID NO 782, SEQ ID NO 783, SEQ ID NO 784, SEQ ID NO 785, SEQ ID NO 786, SEQ ID NO 787, SEQ ID NO 788, SEQ ID NO 789, SEQ ID NO 790, SEQ ID NO 791, SEQ ID NO 792, SEQ ID NO 793, SEQ ID NO 794, SEQ ID NO 795, SEQ ID NO 796, SEQ ID NO 797, SEQ ID NO 798, SEQ ID NO 799, SEQ ID NO 800, SEQ ID NO 801, SEQ ID NO 802, SEQ ID NO 803, SEQ ID NO 804, SEQ ID NO 805, SEQ ID NO 806, SEQ ID NO 807, SEQ ID NO 808, SEQ ID NO 809, SEQ ID NO 810, SEQ ID NO 811, SEQ ID NO 812, SEQ ID NO 813, SEQ ID NO 814, SEQ ID NO 815, SEQ ID NO 816, SEQ ID NO 817, SEQ ID NO 818, SEQ ID NO 819, SEQ ID NO 820, SEQ ID NO 821, SEQ ID NO 822, SEQ ID NO 823, SEQ ID NO 824, SEQ ID NO 825, SEQ ID NO 826, SEQ ID NO 827, SEQ ID NO 828, SEQ ID NO 829, SEQ ID NO 830, SEQ ID NO 831, SEQ ID NO 832, SEQ ID NO 833, SEQ ID NO 834,SEQ ID NO 835, SEQ ID NO 836, SEQ ID NO 837, SEQ ID NO 838, SEQ ID NO 839, SEQ ID NO 840, SEQ ID NO 841, SEQ ID NO 842, SEQ ID NO 843, SEQ ID NO 844, SEQ ID NO 845, SEQ ID NO 846, SEQ ID NO 847, SEQ ID NO 848, SEQ ID NO 849, SEQ ID NO 850, SEQ ID NO 851, SEQ ID NO 852, SEQ ID NO 853, SEQ ID NO 854, SEQ ID NO 855, SEQ ID NO 856, SEQ ID NO 857, SEQ ID NO 858, SEQ ID NO 859, SEQ ID NO 860, SEQ ID NO 861, SEQ ID NO 862, SEQ ID NO 863, SEQ ID NO 864, SEQ ID NO 865, SEQ ID Petição 870250039936, de 15 / 05 / 2025, pág. 41 / 65 7 / 10 NO 866, SEQ ID NO 867, SEQ ID NO 868, SEQ ID NO 869, SEQ ID NO 870, SEQ ID NO 871, SEQ ID NO 872, SEQ ID NO 873, SEQ ID NO 874, SEQ ID NO 875, SEQ ID NO 876, SEQ ID NO 877, SEQ ID NO 878, SEQ ID NO 879, SEQ ID NO 880, SEQ ID NO 881, SEQ ID NO 882, SEQ ID NO 883, SEQ ID NO 884, SEQ ID NO 885, SEQ ID NO 886, SEQ ID NO 887, SEQ ID NO 888, SEQ ID NO 889, SEQ ID NO 890, SEQ ID NO 891, SEQ ID NO 892, SEQ ID NO 893, SEQ ID NO 894, SEQ ID NO 895, SEQ ID NO 896, SEQ ID NO 897,SEQ ID NO 898, SEQ ID NO 899, SEQ ID NO 900, SEQ ID NO 901, SEQ ID NO 902, SEQ ID NO 903, SEQ ID NO 904, SEQ ID NO 905, SEQ ID NO 906, SEQ ID NO 907, SEQ ID NO 908, SEQ ID NO 909, SEQ ID NO 910, SEQ ID NO 911, SEQ ID NO 912, SEQ ID NO 913, SEQ ID NO 914, SEQ ID NO 915, SEQ ID NO 916, SEQ ID NO 917, SEQ ID NO 918, SEQ ID NO 919, SEQ ID NO 920, SEQ ID NO 921, SEQ ID NO 922, SEQ ID NO 923, SEQ ID NO 924, SEQ ID NO 925, SEQ ID NO 926, SEQ ID NO 927, SEQ ID NO 928, SEQ ID NO 929, SEQ ID NO 930, SEQ ID NO 931, SEQ ID NO 932, SEQ ID NO 933, SEQ ID NO 934, SEQ ID NO 935, SEQ ID NO 936, SEQ ID NO 937, SEQ ID NO 938, SEQ ID NO 939, SEQ ID NO 940, SEQ ID NO 941, SEQ ID NO 942, SEQ ID NO 943, SEQ ID NO 944, SEQ ID NO 945, SEQ ID NO 946, SEQ ID NO 947, SEQ ID NO 948, SEQ ID NO 949, SEQ ID NO 950, SEQ ID NO 951, SEQ ID NO 952, SEQ ID NO 953, SEQ ID NO 954, SEQ ID NO 955, SEQ ID NO 956, SEQ ID NO 957, SEQ ID NO 958, SEQ ID NO 959, SEQ ID NO 960, SEQ ID NO 961, SEQ ID NO 962, SEQ ID NO 963,SEQ ID NO 964, SEQ ID NO 965, SEQ ID NO 966, SEQ ID NO 967, SEQ ID NO 968, SEQ ID NO 969, SEQ ID NO 970, SEQ ID NO 971, SEQ ID NO 972, SEQ ID NO 973, SEQ ID NO 974, SEQ ID NO 975, SEQ ID NO 976, SEQ ID NO 977, SEQ ID NO 978, SEQ ID NO 979, SEQ ID NO 980, SEQ ID NO 981, SEQ ID NO 982, SEQ ID NO 983, SEQ ID NO 984, SEQ ID NO 985, SEQ ID NO 986, SEQ ID NO 987, SEQ ID NO 988, SEQ ID NO 989, SEQ ID NO 990, SEQ ID NO 991, SEQ ID NO 992, SEQ ID NO 993, SEQ ID NO 994, SEQ ID NO 995, SEQ ID NO 996, SEQ ID NO 997, SEQ ID NO 998, SEQ ID NO 999, SEQ ID NO 1000, SEQ ID NO 1001, SEQ ID NO 1002, SEQ ID NO 1003, SEQ ID NO 1004, SEQ ID NO 1005, SEQ ID NO 1006, SEQ ID NO 1007, SEQ ID NO 1008, SEQ ID NO 1009, SEQ ID NO 1010, SEQ ID NO 1011, SEQ ID NO Petição 870250039936, de 15 / 05 / 2025, pág. 42 / 65 8 / 10 1012, SEQ ID NO 1013, SEQ ID NO 1014, SEQ ID NO 1015, SEQ ID NO 1016, SEQ ID NO 1017, SEQ ID NO 1018, SEQ ID NO 1019, SEQ ID NO 1020, SEQ ID NO 1021, SEQ ID NO 1022, SEQ ID NO 1023, SEQ ID NO 1024,SEQ ID NO 1025, SEQ ID NO 1026, SEQ ID NO 1027, SEQ ID NO 1028, SEQ ID NO 1029, SEQ ID NO 1030, SEQ ID NO 1031, SEQ ID NO 1032, SEQ ID NO 1033, SEQ ID NO 1034, SEQ ID NO 1035, SEQ ID NO 1036, SEQ ID NO 1037, SEQ ID NO 1038, SEQ ID NO 1039, SEQ ID NO 1040, SEQ ID NO 1041, SEQ ID NO 1042, SEQ ID NO 1043, SEQ ID NO 1044, SEQ ID NO 1045, SEQ ID NO 1046, SEQ ID NO 1047, SEQ ID NO 1048, SEQ ID NO 1049, SEQ ID NO 1050, SEQ ID NO 1051, SEQ ID NO 1052, SEQ ID NO 1053, SEQ ID NO 1054, SEQ ID NO 1055, SEQ ID NO 1056, SEQ ID NO 1057, SEQ ID NO 1058, SEQ ID NO 1059, SEQ ID NO 1060, SEQ ID NO 1061, SEQ ID NO 1062, SEQ ID NO 1063, SEQ ID NO 1064, SEQ ID NO 1065, SEQ ID NO 1066, SEQ ID NO 1067, SEQ ID NO 1068, SEQ ID NO 1069, SEQ ID NO 1070, SEQ ID NO 1071., 2. OLIGONUCLEOTÍDEO ANTISSENSO (ASOs) MODIFICADO, de acordo com a reivindicação 1, caracterizado pelo fato de que a modificação é do tipo fosforotioato.

3. MODIFIED ANTISENSE OLIGONUCLEOTIDE (ASOs), according to claim 1, characterized in that the sequence is preferably SEQ ID NO 150 or SEQ ID NO 1045.

4. NANOPARTICLE characterized by comprising a natural biopolymer and / or a synthetic polymer and an oligonucleotide described in any one of claims 1 to 3.

5. NANOPARTICLE according to claim 4 characterized in that the natural biopolymer is selected from the group: chitosan, alginate, carrageenan, gellan gum, gelatin, casein, agarose, hydroxypropylmethylcellulose.

6. NANOPARTICLE according to claim 5 characterized in that the natural biopolymer is chitosan. Petition 870250039936, dated 05 / 15 / 2025, page 43 / 65 9 / 10 7. NANOPARTICLE according to claim 4 characterized in that the synthetic polymer is selected from the group: polyethylene glycol (PEG), poly(acrylic acid) (PAA), poly(vinyl alcohol) (PVA), carboxylate-containing polymers.

8. NANOPARTICLE according to claim 7 characterized in that the synthetic polymer is preferably polyethylene glycol 9. A COMPOSITION FOR CONTROLLING PLANT DISEASES characterized by comprising an oligonucleotide as described in any one of claims 1 to 3 or a nanoparticle described in any one of claims 4 to 8.

10. METHOD FOR OBTAINING A CARRIER NANOPARTICLE, characterized by comprising the following steps: a. Synthesizing the antisense oligonucleotide as described in any one of claims 1 to 3; b. Solubilizing the natural biopolymer in an acidified aqueous reaction medium; c. Adding to the solution obtained in “b” the oligonucleotides selected in “a” to a concentration of 0.1 to 10 μM; d. Adding to the solution obtained in “c” a polyanion solution to achieve ionic gelation; e. Maintaining the suspension obtained in “d” under magnetic stirring; f. Adding to the solution obtained in “e” synthetic polymer.

11. METHOD FOR OBTAINING A NANOPARTICLE, according to claim 10, characterized in that the natural biopolymer is selected from, but not limited to: chitosan, alginate, carrageenan, gellan gum, gelatin, casein, agarose, hydroxypropylmethylcellulose and various others. Also, but not limited to these, synthetic polymers such as polyethylene glycol (PEG), poly(acrylic acid) (PAA), poly(vinyl alcohol) (PVA), and polymers containing carboxylates may be used. Petition 870250039936, dated 05 / 15 / 2025, page 44 / 65 10 / 10 12. METHOD FOR OBTAINING A NANOPARTICLE, according to claim 11, characterized in that the natural biopolymer is chitosan.

13. METHOD FOR OBTAINING A NANOPARTICLE, according to claim 11, characterized in that the synthetic polymer is polyethylene glycol.

14. USE OF MODIFIED ANTISENSE OLIGONUCLEOTIDE (ASOs), as defined in any of claims 1 to 3, characterized by being for the control of bacterial spot of tomato (MBT) Petition 870250039936, dated 05 / 15 / 2025, p. 45 / 65

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