WO2025262056A1 - Method of controlling pests with a composition comprising valifenalate and cyazofamid - Google Patents

Method of controlling pests with a composition comprising valifenalate and cyazofamid

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Publication number
WO2025262056A1
WO2025262056A1 PCT/EP2025/066929 EP2025066929W WO2025262056A1 WO 2025262056 A1 WO2025262056 A1 WO 2025262056A1 EP 2025066929 W EP2025066929 W EP 2025066929W WO 2025262056 A1 WO2025262056 A1 WO 2025262056A1
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WIPO (PCT)
Prior art keywords
composition
valifenalate
cyazofamid
plant
applying
Prior art date
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French (fr)
Inventor
Audrey DERUMIER
Ed BINGHAM
Paul RUELENS
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Certis Belchim BV
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Certis Belchim BV
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Publication of WO2025262056A1 publication Critical patent/WO2025262056A1/en
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Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/12Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, neither directly attached to a ring nor the nitrogen atom being a member of a heterocyclic ring
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/501,3-Diazoles; Hydrogenated 1,3-diazoles
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01PBIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00Fungicides

Definitions

  • the invention relates to a method of improving plant resistance against pests and/or inducing plant defense pathways with a composition comprising valifenalate and cyazofamid. More in particular, the invention relates to a method of controlling carboxylic acid amide (CAA) resistant pests.
  • CAA carboxylic acid amide
  • Oomycetes which include notorious genera such as Phytophthora, Plasmopara, and Pseudoperonospora, are responsible for significant economic losses globally due to their ability to rapidly infect and devastate a wide variety of crops.
  • Traditional methods for controlling these pathogens include cultural practices, resistant cultivars, and the application of chemical fungicides.
  • CAA carboxylic acid amides
  • the present invention aims to resolve at least some of the problems mentioned above. It is furthermore an object of the present invention to provide pesticide compositions as alternatives to the prior art, or as improvements thereof.
  • a first aspect of the present invention provides a method of controlling pests according to claim 1.
  • the method of the first aspect was found to be effective in controlling at least one organism chosen from the group of oomycetes, and showed consistent results over a broad range of organisms within this group.
  • the management of oomycete infections is particularly challenging, partly due to their ability to develop resistance to certain classes of pesticides, such as carboxylic acid amides (CAA). Resistances can generally lead to reduced efficacy of the pesticide, necessitating higher doses or more frequent applications, and often prompting the use of alternative or combination treatments to manage resistant strains effectively.
  • the method of the invention unexpectedly showed improved efficacy without needing to increase dosage or application rates and was able to effectively combat a broad range of oomycetes.
  • Further aspects of the invention relate to a method of improving plant resistance against pests and/or inducing plant defense pathways according to claim 14, and to a fungicidal composition according to claim 27.
  • the method according to the third aspect of the invention allows that a target crop plant effectively obtains a better resistance against pest infestations and/or that plant defense pathways are induced in the target crop plant, which actively helps in fighting off pest infestations.
  • the herein described resistance and/or pathways provide an alternative or additional mode of action against pests, allowing the crop plant to better thrive in its habitat by preventing, mitigating or withstanding any possible damage or negative effects caused by pests.
  • the present invention concerns a method of controlling pests with a composition comprising valifenalate and cyazofamid.
  • a compartment refers to one or more than one compartment.
  • % by weight refers to the relative weight of the respective component based on the overall weight of the formulation.
  • weight percent refers to the relative weight of the respective component based on the overall weight of the formulation.
  • at least one refers to the relative weight of the respective component based on the overall weight of the formulation.
  • the term encompasses inter alia a reference to any one of said members, or to any two or more of said members, such as, e.g., any >3, >4, >5, >6 or >7 etc. of said members, and up to all said members.
  • a first aspect of the present invention relates to a method of controlling pests, said method comprising: providing a composition comprising valifenalate and cyazofamid, and applying said composition to a crop plant, a pest population associated with a crop plant, a habitat of a crop plant, or a combination thereof, wherein said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1:5, and wherein said pest population comprises at least one organism chosen from the group of oomycetes.
  • pests are organisms that directly or indirectly harm crops by feeding on plant tissues, transmitting diseases, or competing with crops for nutrients, water, and light. Pests can cause significant economic losses by reducing crop yields, affecting the quality of produce, and increasing production costs due to the need for pest management practices.
  • Effective pest control generally involves integrated pest management (IPM) strategies that combine biological, chemical, cultural, and mechanical methods to minimize pest populations and their impact while promoting sustainable agricultural practices.
  • the pests according to the method of the invention are preferably organisms chosen from the class of oomycetes.
  • Crop plant need to be understood as any plant species that is cultivated intentionally for the purpose of harvesting a product of economic value.
  • Crop plants are grown extensively in agriculture for various uses, including food (such as cereals, fruits, vegetables), feed (for livestock), fiber (such as cotton, hemp), oil (such as soybeans, sunflower), biomass (for biofuel production), medicinal substances (such as herbs, pharmaceuticals), and ornamental purposes.
  • Crop plants are selected based on their suitability to specific climatic, soil, and environmental conditions, and they are managed through agricultural practices such as planting, irrigation, fertilization, pest control, and harvesting to optimize growth and yield.
  • the choice of crop plant may be influenced by market demand, economic considerations, and the adaptability of the plant to local growing conditions.
  • This habitat includes various physical, chemical, and biological factors that influence the growth, development, and productivity of the crop.
  • Key components of the habitat of a crop plant may include soil type (texture, structure, fertility, pH), climate (temperature, precipitation, humidity, sunlight), water availability (irrigation practices, rainfall), and the presence of other organisms (beneficial insects, pests, weeds, microorganisms).
  • the habitat may also encompass the agricultural practices and management techniques employed by farmers to create optimal growing conditions for the crop. Understanding the habitat of a crop plant is important for making informed decisions about crop selection, planting schedules, pest and disease management, and sustainable farming practices to ensure high yields and quality produce.
  • valifenalate is directed to a carboxylic acid amide (CAA) fungicide. It mainly functions by inhibiting the cellulose synthase enzyme, which is crucial for the cell wall synthesis in some organisms, such as oomycetes. This inhibition disrupts the formation of the cell wall, leading to the death of the cell. Valifenalate has been used against oomycete pathogens in various crops, including grapes, potatoes, and tomatoes. It is known for its systemic action, allowing it to be absorbed and translocated within the plant, providing protection to new growth.
  • CAA carboxylic acid amide
  • valifenalate can be represented by its IUPAC name: 2-(2-(l-(4-chlorophenyl)-3-(4-methylphenyl)ureido)-3,3-dimethylbutan- amido)-2-methylpropanoic acid methyl ester.
  • Cyazofamid refers to a fungicide belonging to the cyano-imidazole chemical group. It mainly acts by inhibiting complex III (cytochrome bcl complex) in the mitochondrial electron transport chain of oomycetes, thereby disrupting cellular respiration and energy production. This mode of action is effective against a wide range of oomycete diseases, including downy mildew and late blight. Cyazofamid is known for its protective and curative properties, making it a valuable component in various integrated pest management programs.
  • cyazofamid The chemical structure of cyazofamid is denoted by its IUPAC name: 4-chloro-2-cyano-N,N- dimethyl-5-(4-methylphenyl)-lH-imidazole-l-sulfonamide.
  • oomycetes also known as water molds
  • fungus-like organisms classified under the kingdom Stramenopiles are characterized by their filamentous, coenocytic hyphae and cell walls made of cellulose rather than chitin, which distinguishes them from true fungi.
  • Oomycetes include many plant pathogenic species, such as those causing downy mildew and root rot. Notable genera include Phytophthora, Plasmopara, Pythium, and Aphanomyces. These pathogens are notorious for causing severe agricultural losses due to their ability to rapidly spread and infect a wide range of host plants.
  • the "group of oomycetes” may also be referred to as the "class of oomycetes".
  • said pest population thus comprises at least one organism chosen from the class of oomycetes.
  • the method of the invention was found to be effective in controlling at least one organism chosen from the group of oomycetes, and showed consistent results over a broad range of organisms within this group.
  • the management of oomycete infections is particularly challenging, partly due to their ability to develop resistance to certain classes of pesticides, such as carboxylic acid amides (CAA). Resistances can generally lead to reduced efficacy of the pesticide, necessitating higher doses or more frequent applications, and often prompting the use of alternative or combination treatments to manage resistant strains effectively.
  • the method of the invention unexpectedly showed improved efficacy without needing to increase dosage or application rates and was able to effectively combat a broad range of oomycetes.
  • a synergistic effect in pesticides is always present when the pesticide action of the active compound combination exceeds the action of the active compounds when applied individually.
  • X is the amount of damage (expressed in %) done by pesticide A at an application rate of m g/ha,
  • E is the expected amount of damage (expressed in %) done by the combination of pesticides A and B at their respective application rates of m and n g/ha.
  • the wording "amount of damage” may in the light of the present invention also be read as “amount of disease control” or “amount of efficacy”, which alternative wordings may read more appropriately in the context of fungicidal activity. Similarly in this context, the wording "damage” may also be read as “disease control” or "efficacy”.
  • the activity of the combination is super additive, i.e. it shows a synergistic effect.
  • the damage actually observed must exceed the values calculated using the above formulae for the expected damage E.
  • the Colby calculation can be similarly used to indicate an "antagonistic effect", or to indicate a merely "additive effect" between compounds.
  • the activity of the combination is antagonistic.
  • the activity of the combination is merely additive.
  • Colby is often formulated for herbicides, its general teachings may extend to all kinds of pesticides.
  • carboxylic acid amide (CAA) fungicides and fungicides belonging to the cyano-imidazole chemical group in some instances may exhibit an antagonistic effect when used in combination.
  • the required dosages or application rates of carboxylic acid amide (CAA) fungicides and fungicides belonging to the cyano-imidazole chemical group may need to be increased in order to provide adequate or effective control.
  • the combination of valifenalate and cyazofamid in the ratios as described herein allowed to reduce the antagonistic effect which is commonly observed.
  • the antagonistic effect is reduced by at least 1 %. More by preference, the antagonistic effect is reduced by at least 2 %, at least 3 %, at least 4 %, or at least 5 %. Even more by preference, the antagonistic effect is reduced by at least 10 %, at least 15 %, or at least 20 %.
  • the method of the invention thus unexpectedly showed improved efficacy without needing to increase dosage or application rates and was able to effectively combat a broad range of oomycetes.
  • said pest population comprises at least one organism chosen from the group of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
  • Phytophthora relates to a genus within the oomycetes, encompassing several species known for their negative impact on agriculture. Species like Phytophthora infestans, for example, cause late blight in potatoes and tomatoes, while Phytophthora capsici may affect peppers and cucurbits. These pathogens mostly thrive in moist environments and are characterized by their production of sporangia and zoospores, which facilitate rapid dissemination. Control of Phytophthora is challenging due to their resilience and ability to survive in soil and plant debris for extended periods of time.
  • Bremia need to be understood as a genus of oomycetes that primarily affects lettuce and other leafy vegetables, for example causing downy mildew (Bremia lactucae). This pathogen generally thrives in cool, humid conditions and can cause significant crop losses by reducing photosynthesis and promoting secondary infections. Bremia produces sporangia on sporangiophores, which emerge from stomata on the undersides of leaves, giving a white, downy appearance. Common control strategies for Bremia include the use of fungicides, resistant varieties, and environmental management to minimize leaf wetness.
  • Pseudoperonospora is a genus of oomycetes that includes species such as Pseudoperonospora cubensis, the causative agent of downy mildew in cucurbits. This pathogen is highly destructive and can rapidly defoliate plants, leading to reduced yields and fruit quality. Pseudoperonospora produces sporangia that are dispersed by wind and rain, facilitating widespread infection. Common management practices involve the application of fungicides, crop rotation, and the use of resistant cultivars.
  • Peronospora is a genus of oomycetes known for causing downy mildew diseases in a variety of host plants, including ornamentals, vegetables, and legumes. Species like Peronospora farinosa affect spinach, while Peronospora sparsa infects roses. These pathogens produce sporangia on the surface of infected plant tissues, leading to a characteristic downy appearance. Control of Peronospora commonly involves the use of fungicides, resistant plant varieties, and cultural practices to reduce the incidence of infection.
  • the method as described herein effectively allows to control each of the discussed oomycetes genera, preferably by implementing less complex control strategies than those know in the art. It was observed that the method improved efficacy without needing to increase dosage or application rates, and was able to effectively combat several genera within the group of oomycetes that are notorious for being the most difficult to control.
  • said pest population thus comprises at least one organism chosen from the genus of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
  • said pest population comprises at least one organism chosen from the group of Phytophthora infestans, Phytophthora capsica, Phytophthora sojae, Phytophthora ramorum, Phytophthora cinnamon, Plasmopara viticola, Bremia lactucae, Pseudoperonospara cubensis, Peronospora farinose, Peronospora sparsa, or combinations thereof.
  • Plantophthora infestans is a highly destructive oomycete pathogen responsible for late blight in potatoes and tomatoes, among other crops. It is characterized by its ability to cause rapid and severe foliar blight, stem lesions, and tuber rot, leading to significant yield losses. The pathogen thrives in cool, moist conditions and can spread quickly via wind-dispersed sporangia. Common control measures include the use of resistant cultivars, fungicides, and cultural practices to reduce moisture on plant surfaces.
  • Plantophthora capsica is an aggressive pathogen that causes root, crown, and fruit rot in a wide range of vegetable crops, including peppers, cucurbits, and tomatoes. This oomycete thrives in warm, wet environments and can survive in soil and plant debris for extended periods. Infected plants exhibit symptoms such as wilting, stunted growth, and fruit rot. Common management strategies include crop rotation, the use of resistant varieties, soil drainage improvement, and fungicide applications.
  • “Phytophthora sojae” is an oomycete responsible for causing Phytophthora root and stem rot in soybeans. This pathogen infects soybean plants at all growth stages, leading to damping-off, root rot, stem cankers, and ultimately plant death. Phytophthora sojae thrives in waterlogged soils and spreads through soil and water. Common control involves using resistant soybean cultivars, improving soil drainage, and applying fungicides where resistance management practices are necessary.
  • Phytophthora ramorum is the causal agent of sudden oak death and ramorum blight, affecting a variety of trees and ornamental plants. This pathogen is notorious for causing extensive mortality in oak and tanoak trees, which are prevalent in North America. Symptoms include leaf spots, shoot dieback, and bark cankers that exude a dark, sticky sap. Phytophthora ramorum spreads through infected plant material, soil, and water. Common control measures include sanitation practices, removal of infected plants, and regulatory quarantine to prevent spread.
  • Phytophthora cinnamomi is a soil-borne oomycete that causes root rot in a very broad range of plant species, including many agricultural and horticultural crops. It leads to root necrosis, reduced water and nutrient uptake, wilting, and plant death. This pathogen is particularly destructive in avocado, chestnut, and eucalyptus plantations. Common control methods include improving soil drainage, applying fungicides, and using resistant rootstocks.
  • Plasmopara viticola is an oomycete responsible for downy mildew in grapevines. It causes yellowish, oily spots on the upper leaf surface and white, downy growth on the underside. Severe infections can lead to defoliation, reduced photosynthesis, and poor fruit quality. Plasmopara viticola generally thrives in warm, humid conditions and spreads through sporangia dispersed by wind and rain. Common management includes fungicide applications, canopy management to improve air circulation, and the use of resistant grape varieties.
  • Bremia lactucae is an oomycete that causes downy mildew in lettuce. Infected plants exhibit yellowing and chlorosis of leaves, along with white, downy fungal growth on the undersides. This pathogen can cause significant crop losses in both field and greenhouse environments. Bremia lactucae mainly spreads through airborne sporangia and requires cool, humid conditions for infection. Control measures include resistant cultivars, fungicides, and environmental management to reduce leaf wetness.
  • Pseudoperonospora cubensis is an oomycete responsible for downy mildew in cucurbits, including cucumbers, melons, and squash. Symptoms include angular, yellow lesions on leaves that become necrotic, leading to defoliation and reduced yield. The pathogen spreads through wind-dispersed sporangia and thrives in warm, humid conditions. Management strategies include fungicide applications, resistant varieties, and crop rotation to reduce inoculum levels.
  • Peronospora farinosa is an oomycete that causes downy mildew in spinach and other leafy vegetables. Infected plants display yellowing, chlorosis, and a grayish, downy growth on the undersides of leaves. This pathogen mainly spreads through wind-borne spores and requires cool, moist conditions for infection. Control measures include using resistant cultivars, applying fungicides, and practicing good field sanitation.
  • Peronospora sparsa is an oomycete responsible for downy mildew in roses and other ornamentals. Symptoms include yellowing and spotting on leaves, with a white to grayish fungal growth on the undersides. This pathogen commonly spreads through airborne sporangia and thrives in cool, moist environments. Common management includes fungicide applications, removing infected plant material, and ensuring good air circulation around plants.
  • the method as described herein allows to effectively control each of the aforementioned oomycetes in a very wide range of crops. Efficacy was found to be consistently high, especially in comparison to management strategies making use of fungicide components as known in the art. The method thus allows to significantly reduce the complexity of existing pest management strategies.
  • said pest population thus comprises at least one organism chosen from the species of Phytophthora infestans, Phytophthora capsica, Phytophthora sojae, Phytophthora ramorum, Phytophthora cinnamon, Plasmopara viticola, Bremia lactucae, Pseudoperonospara cubensis, Peronospora farinose, Peronospora sparsa, or combinations thereof.
  • said pest population comprises at least one strain which is carboxylic acid amide (CAA) resistant.
  • CAA carboxylic acid amide
  • CAA resistant organisms relate to those organisms that have developed resistance to fungicides within the CAA class, such as valifenalate and dimethomorph. Resistance is often due to genetic mutations that alter the target site of the fungicide, reducing its efficacy. These resistant organisms can thus better survive and proliferate despite fungicide applications, making disease management more difficult. In current practices, monitoring for resistance and using integrated pest management strategies are essential to mitigate the impact of CAA resistance.
  • the method as described herein was found to be surprisingly effective in controlling a wide variety of oomycetes, even those that have developed CAA resistance. Not only does this allow to improve controlling CAA resistant organisms, it also means that the method can be used in management strategies targeting a broad scope of oomycetes. Therefore, management strategies may be significantly simplified and the herein described method may be effectively applicable to most infestations of oomycetes.
  • said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 1,1.
  • RF resistance factor
  • CAA carboxylic acid amide
  • resistance factor in light of the invention towards at least one carboxylic acid amide (CAA), refers to a quantitative measure of the degree of resistance that a pest population has developed, particularly a quantitative measure of the degree of resistance that oomycetes have developed against fungicides in the carboxylic acid amide class.
  • the resistance factor is calculated in laboratory assay by comparing the effective concentration (ECso) of a pesticide, which is the concentration required to inhibit 50 % of the pest population, in a resistant strain to the EC50 required for a sensitive, non-resistant strain. Mathematically, this may be expressed as:
  • Resistance factor (RF) EC50 of resistant strain I EC50 of non-resistant strain.
  • An RF value of 1 indicates no resistance, meaning the fungicide is equally effective against both strains. Higher RF values indicate a greater degree of resistance, with an RF value of 10 meaning that the resistant strain requires ten times the concentration of the fungicide to achieve the same level of control as the sensitive strain. This metric is crucial for understanding the extent of fungicide resistance in pest populations and for developing effective resistance management strategies.
  • the pest populations referred to herein are assessed in the form of pest isolates.
  • the resistant pest population is represented by an isolate of a resistant strain
  • the non-resistant pest population is represented by an isolate of a non-resistant strain.
  • the non-resistant pest population is represented by a plurality of isolates of non-resistant strains. This approach allows for the determination of a baseline resistance factor (RF) for the non-resistant population. More preferably, the non- resistant pest population is represented by at least 20 isolates of non-resistant strains. Even more preferably, the non-resistant pest population is represented by at least 30, 40, 50, 60, 70, 80, 90, 100, 125, or even 150 isolates of non-resistant strains.
  • RF resistance factor
  • the method as described herein was found to be surprisingly effective in controlling a wide variety of oomycetes, including those with a resistance factor (RF) of at least 1,1 towards carboxylic acid amides (CAA).
  • RF resistance factor
  • CAA carboxylic acid amides
  • said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 1,2, more by preference of at least 1,3, 1,4, or 1,5. Even more by preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 2, 3, 4, 5, 6, 7, 8, or 9,0. Even more by preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 10. Even more by preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.
  • the non-resistant pest population is represented by a plurality of isolates of non-resistant strains, wherein the determined baseline resistance factor (RF) exhibits a variance within a predefined range, preferably a predefined range of [-10; + 10], [-20;+20], [- 30; + 30], [-40;+40], or even [-50; + 50].
  • RF baseline resistance factor
  • said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 50, 100, 250, 500, 1000, 5000, 10000, 20000, 30000, or 40000, or even 50000.
  • RF resistance factor
  • CAA carboxylic acid amide
  • said pest population having a resistance factor according to any of the foregoing embodiments is a pest isolate.
  • said carboxylic acid amide (CAA) fungicide is chosen from the group of valifenalate, dimethomorph, flumorph, pyrimorph, benthiavalicarb, iprovalicarb, mandipropamid, or combinations thereof.
  • dimethomorph is a systemic fungicide belonging to the carboxylic acid amide (CAA) class, used primarily to control oomycete pathogens such as downy mildew and late blight. It acts by inhibiting the biosynthesis of sterols in the cell membranes of fungi, disrupting cell wall formation and leading to the death of the pathogen. Dimethomorph is used both as a preventative and curative treatment, with good translaminar and systemic movement within the plant.
  • the chemical structure of dimethomorph can be represented by its IUPAC name: (E,Z)- 4-(3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)acryloyl)morpholine.
  • Flumorph is a fungicide used to control oomycetes, particularly in crops such as potatoes, tomatoes, and grapes. It generally works by disrupting the formation of the fungal cell wall, thereby inhibiting the growth and spread of the pathogen. Flumorph is known for its protective action, making it effective when applied before the onset of disease. Its chemical structure can be denoted by its IUPAC name: 3- (3,5-dichlorophenyl)-2-methoxy-4-(trifluoromethyl)phenyl methanesulfonate.
  • Pyrimorph is a fungicide that belongs to the CAA class and is used to control a variety of oomycete pathogens, including Phytophthora infestans, which causes late blight in potatoes and tomatoes. It acts by inhibiting the synthesis of cell wall components in the pathogens, thereby preventing their growth and reproduction. Pyrimorph is used both as a curative and preventive treatment.
  • the chemical structure of pyrimorph is represented by its IUPAC name: 4-(2-chlorobenzyl)-N- (l,l-dimethyl-2-propynyl)-pyrimidin-5-amine.
  • Benthiavalicarb is to be read as a fungicide used to control oomycete diseases such as downy mildew and late blight in various crops. It belongs to the carboxylic acid amide (CAA) class and works by inhibiting the biosynthesis of cellulose in the cell walls of the pathogens, leading to their death. Benthiavalicarb is known for its systemic properties, providing both protective and curative effects.
  • CAA carboxylic acid amide
  • benthiavalicarb can be described by its IUPAC name: (RS)-2-(l- ⁇ [l-(4-chlorophenyl)ethyl]amino ⁇ ethylidene)-4-ethyl-5- methyl-3-thiophenecarboxylic acid methyl ester.
  • Iprovalicarb is a systemic fungicide used to control oomycete pathogens such as downy mildew, late blight, and other related diseases in various crops. It acts by inhibiting the synthesis of key components in the cell walls of the pathogens, thereby preventing their growth and spread. Iprovalicarb is effective when used as a preventative treatment and can be applied to a wide range of crops. Its chemical structure is represented by its IUPAC name: (RS)-2-methyl-l- ⁇ [l-(4- isopropylphenyl)ethyl]amino ⁇ carbonyl ⁇ cyclopropane-l-carboxylic acid.
  • mandipropamid is a fungicide belonging to the carboxylic acid amide (CAA) class, used primarily to control oomycete pathogens such as downy mildew and late blight. It acts by inhibiting the biosynthesis of cellulose in the cell walls of the pathogens, leading to their death. Mandipropamid is known for its systemic and translaminar activity, providing both protective and curative effects. The chemical structure of mandipropamid is described by its IUPAC name: (RS)-2- ⁇ (2,6-dimethylphenyl)-methoxyacetylamino ⁇ -propionic acid methyl ester.
  • CAA carboxylic acid amide
  • CAA carboxylic acid amide
  • said valifenalate and said cyazofamid are present in said composition according to a ratio of between 8: 1 and 1:4.
  • said valifenalate and said cyazofamid are present in said composition according to a ratio of between 6: 1 and 1:3, more by preference of between 4: 1 and 1 :2, even more by preference of between 3: 1 and 1 : 1.
  • the method was found to be more effective in controlling oomycete infestations such as described herein. Especially oomycete infestation encompassing CAA resistant strains, or even oomycete infestations encompassing both CAA resistant and CAA non-resistant strains, were found the be effectively controlled.
  • said composition comprises: from 10 to 50 wt.% of valifenalate, and from 5 to 25 wt.% of cyazofamid, based on the total weight of the composition.
  • compositions comprising from 10 to 50 wt.% of valifenalate and from 5 to 25 wt.% of cyazofamid demonstrated enhanced efficacy against oomycetes, by preference CAA-resistant oomycetes.
  • This combination not only improves control over CAA-resistant strains but also allows for a versatile management strategy targeting a broad spectrum of oomycetes without the need to differentiate based on resistance profiles. Consequently, management strategies can be significantly simplified, making the described method broadly applicable and highly effective for most oomycete infestations.
  • said composition comprises from 5 to 80 wt.% of valifenalate, based on the total weight of the composition.
  • said composition comprises from 10 to 60 wt.% of valifenalate, based on the total weight of the composition. More by preference, said composition comprises from 10 to 20 wt.% of valifenalate, based on the total weight of the composition.
  • said composition comprises from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition.
  • said composition comprises from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
  • said composition comprises from 5 to 80 wt.% of valifenalate, and from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 10 to 60 wt.% of valifenalate, and from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. Even more by preference, said composition comprises from 10 to 20 wt.% of valifenalate, and from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
  • said composition is formulated as a suspension concentrate (SC), an oil dispersion (OD), as a water dispersible granules (WG), as an emulsifiable concentrate (EC), as a concentrated oil-in-water emulsion (EW) as a wettable powder (WP), as a micro-emulsion (ME), as a capsule suspension (CS), as a suspoemulsion (SE), or as a mixed formulation of CS and SC (ZC).
  • SC suspension concentrate
  • OD oil dispersion
  • WG water dispersible granules
  • EW emulsifiable concentrate
  • EW concentrated oil-in-water emulsion
  • ME micro-emulsion
  • CS capsule suspension
  • SE suspoemulsion
  • ZC mixed formulation of CS and SC
  • SC sustained release
  • a “suspension concentrate (SC)” is a type of liquid formulation where finely divided, insoluble active ingredients are suspended in water or another liquid carrier. This formulation is designed to be diluted with water before application, providing a convenient and effective means of delivering the active ingredient to the target pest. SC formulations are stable, easy to handle, and ensure uniform distribution of the active ingredient.
  • oil dispersion OD
  • OD oil dispersion
  • water dispersible granules refers to a formulation consisting of granules to be applied after disintegration and dispersion in water.
  • EC emulsifiable concentrate
  • a “concentrated oil-in-water emulsion (EW)” refers to a fluid, heterogeneous formulation consisting of a solution of pesticide in an organic liquid, dispersed as fine globules in a continuous water phase.
  • wettable powder reads onto a powder formulation to be applied as a suspension after dispersion in water. It forms a suspension rather than a true solution, requiring agitation to stay mixed.
  • a "micro-emulsion (ME)" is a clear, stable, and fine emulsion with droplet sizes significantly smaller than those in a standard emulsion, or more in particular, a clear to opalescent, oil and water containing liquid, to be applied directly or after dilution in water, when it may form a diluted micro-emulsion or a conventional emulsion.
  • capsule suspension (CS) in light of the present invention is to be read as a formulation wherein the active ingredient is encapsulated in tiny, polymeric capsules suspended in a liquid, normally intended for dilution with water before use. This type provides controlled release of the active ingredient, reduced exposure risk, and can enhance stability and effectiveness.
  • a “suspoemulsion (SE)” is a fluid, heterogeneous formulation consisting of a stable dispersion of one or more active ingredients in the form of solid particles, and of fine globules immiscible with water in a continuous water phase.
  • SE suspoemulsion
  • a “mixed formulation of CS and SC (ZC)” is a stable fluid suspension of capsules of one or more active ingredients combined with a suspension of fine particles of one or more active ingredients, normally intended for dilution with water before use.
  • said composition is formulated as a suspension concentrate (SC).
  • SC suspension concentrate
  • SC formulations offer numerous advantages for fungicide compositions in agricultural applications. These formulations may provide improved stability, ensuring that the active ingredient remains evenly dispersed and effective over extended storage periods.
  • the liquid nature of SC formulations may allow for ease of handling, measuring, and mixing, reducing the risk of handling errors compared to dry formulations. This may also ensure uniform distribution of the fungicide when diluted with water, leading to consistent and thorough coverage of the target area. Additionally, SC formulations may eliminate the problem of dust generation, minimizing inhalation risks for applicators and reducing environmental contamination.
  • the finely divided particles in SC formulations may furthermore enhance the bioavailability of the fungicide, promoting better absorption and efficacy against target pathogens.
  • SC formulations may also help mitigate phytotoxicity by reducing the concentration of potentially harmful solvents and adjuvants, ensuring safer application to crops.
  • Compatibility with a wide range of other agricultural chemicals allows for tank-mixing and integrated pest management strategies. The minimized risk of spillage and wastage may make SC formulations more environmentally friendly. Overall, the user safety, environmental benefits, and enhanced performance make SC formulations were found to be an ideal choice for fungicide delivery in agriculture.
  • said composition is formulated as an oil dispersion (OD). According to some other embodiments, said composition is formulated as water dispersible granules (WG). According to some other embodiments, said composition is formulated as an emulsifiable concentrate (EC). According to some other embodiments, said composition is formulated as a concentrated oil-in-water emulsion (EW). According to some other embodiments, said composition is formulated as a wettable powder (WP). According to some other embodiments, said composition is formulated as a micro-emulsion (ME). According to some other embodiments, said composition is formulated as a capsule suspension (CS). According to some other embodiments, said composition is formulated as a suspoemulsion (SE). According to some other embodiments, said composition is formulated as a mixed formulation of CS and SC (ZC).
  • OD oil dispersion
  • WG water dispersible granules
  • EC emulsifiable concentrate
  • EW concentrated oil-in-water emul
  • applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha.
  • active ingredient (Al) refers to the specific chemical or compound in a product that is responsible for its desired or primary effect.
  • the active ingredient is the substance that provides the pesticidal activity. It is distinct from other components of the formulation, such as carriers, solvents, or additives, which are used to enhance the product's stability, application, or safety. Application amounts may thus be expressed in "grams of active ingredient per hectare (g Al/ha)".
  • This broad range ensures flexibility in application, allowing for adjustments based on specific crop requirements and environmental conditions.
  • applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha. Most by preference, applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha. With increased preference, it has been shown that better balance is obtained between efficacy and crop safety, ensuring robust protection against oomycete pathogens.
  • applying said composition comprises applying cyazofamid in an amount of between 50 and 120 g Al/ha.
  • This broad range provides versatility in combating various levels of oomycete infestation.
  • applying said composition comprises applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying cyazofamid in an amount of between 65 and 95 g Al/ha. Most by preference, applying said composition comprises applying cyazofamid in an amount of between 70 and 90 g Al/ha. With increased preference, it has been shown that more effective control is obtained with sustainable application rates, ensuring long-term crop protection and environmental safety.
  • applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha.
  • This combination ensures broad-spectrum control and flexibility in managing various oomycete diseases.
  • applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha, and applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha, and applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha, and applying cyazofamid in an amount of between 65 and 95 g Al/ha.
  • applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha, and applying cyazofamid in an amount of between 70 and 90 g Al/ha.
  • said crop plant is selected from the group of potato crops, tomato crops, (grape)vine crops, cucurbit crops, lettuce crops, ornamental plants, or combinations thereof.
  • Lettuce crops receive protection from Bremia lactucae, which causes downy mildew and can lead to severe crop losses.
  • the embodiment also covers ornamental plants, which are often affected by Peronospora sparsa and other oomycete pathogens, ensuring the health and aesthetic value of these plants in both commercial and domestic settings.
  • the ability to use this method across such a wide range of crops simplifies management strategies and enhances the overall efficacy of oomycete control measures.
  • said crop plant is selected from the group of potato crops.
  • said potato crop is chosen from the group of Solanum tuberosum, Solanum andigenum, Solanum phureja, Solanum stenotomum, Solanum ajanhuiri, or combinations thereof.
  • said crop plant is selected from the group of tomato crops.
  • said tomato crop is chosen from the group of Solanum lycopersicum, Solanum pimpinellifolium, Solanum cheesmaniae, Solanum peruvianum, Solanum habrochaites, or combinations thereof.
  • said crop plant is selected from the group of (grape)vine crops.
  • said (grape)vine crop is chosen from the group of Vitis vinifera, Vitis labrusca, Vitis riparia, Vitis rotundifolia, Vitis amurensis, or combinations thereof.
  • said crop plant is selected from the group of cucurbit crops.
  • said cucurbit crop is chosen from the group ofCucumis sativus, Cucumis melo, Cucurbita pepo, Cucurbita maxima, Cucurbita moschata, Citrullus lanatus, or combinations thereof.
  • said crop plant is selected from the group of lettuce crops.
  • said lettuce crop is chosen from the group of Lactuca sativa, Lactuca sativa var. longifolia, Lactuca sativa var. crispa, Lactuca sativa var. capitata, Lactuca sativa var. angustana, or combinations thereof.
  • said crop plant is selected from the group of ornamental plants.
  • said ornamental plant is chosen from the group of Rosa spp., Chrysanthemum spp., Pelargonium spp., Petunia spp., Impatiens spp., Begonia spp., or combinations thereof.
  • valifenalate and/or cyazofamid are also falling within the above definitions of valifenalate and cyazofamid. Any salt may be possible as long as it is agriculturally acceptable.
  • alkali metal salts such as a sodium salt and a potassium salt
  • alkaline earth metal salts such as a magnesium salt and a calcium salt
  • ammonium salts such as a monomethylammonium salt, a dimethylammonium salt and a triethylammonium salt
  • inorganic acid salts such as a hydrochloride, a perchlorate, a sulfate and a nitrate salt
  • organic acid salts such as an acetate and a methanesulfonate salt.
  • CAA carboxylic acid amide
  • fungicidal activity of fungicides comprising valifenalate or cyazofamid against oomycetes (including various species causing diseases such as late blight, downy mildew, and root rot) is already at a high level, but generally depends on factors such as the application rate, the specific formulation, the particular pathogen being targeted, and the climatic and soil conditions. Additional considerations include the duration of action and breakdown rate of the fungicide, its compatibility with different crop plants, the speed of action, the spectrum of activity, and its behavior towards subsequent crops (replanting issues) or general application flexibility (control of oomycetes at various growth stages).
  • a possible solution to these problems may involve providing combined fungicide compositions, combining multiple fungicides and/or other components from the group of agrochemically active compounds of different types, along with formulation auxiliaries and additives commonly used in crop protection, which contribute desired additional properties.
  • combining multiple active compounds often results in chemical, physical, or biological incompatibilities, such as decomposition of an active compound or antagonism in biological activity. Therefore, potentially suitable combinations of active compounds must be selected carefully and tested experimentally for their suitability, with the possibility of negative or positive outcomes not being safely discounted a priori.
  • Carboxylic acid amide (CAA) fungicides and fungicides belonging to the cyanoimidazole chemical group in some instances may exhibit an antagonistic effect when used in combination.
  • CAA Carboxylic acid amide
  • the combination of valifenalate and cyazofamid has shown an unexpected reduction in antagonistic effects, and an increase in fungicidal activity. This enhanced activity was especially observed when combining valifenalate with cyazofamid according to the herein described weight ratios.
  • the composition comprises at least 1 wt.% of additional components, based on the total weight of the composition. More by preference, the composition comprises at least 5 wt.% of additional components, at least 10 wt.%, or at least 15 wt.% of additional components, based on the total weight of the composition. Even more by preference, the composition comprises at least 20 wt.%, at least 25 wt.%, at least 30 wt.%, at least 40 wt.%, or at least 50 wt.% of additional components, based on the total weight of the composition. According to some embodiments, the composition comprises at least 60 wt.%, at least 70 wt.%, at least 80 wt.%, or even at least 85 wt.% of additional components, based on the total weight of the composition.
  • said additional components are selected from the group comprising other pesticides such as herbicides, insecticides, fungicides, or other active pesticide ingredients, safeners, antioxidants, chemical stabilizers, adhesives, fertilizers, perfumes, colorants, liquid carriers, solid carriers, surfaceactive agents, crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, foaming agents, light-blocking agents, compatibility agents, antifoam agents, sequestering agents, neutralizing agents and buffers, wetting and dispersing agents, preservatives, thickening agents, corrosion inhibitors, freezing point depressants, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants, sticking agents and humectants, such as, for example, propylene glycol.
  • the herbicide composition can also comprise various agrochemically active compounds, for example from the group of the acaricides, nematicides, bird
  • safety is to be understood as a compound or a mixture of compounds which compensates for, or reduces, the phytotoxic properties of a pesticide towards crop plants without substantially reducing its pesticidal action.
  • Non-limiting examples of colorants include inorganic pigments such as iron oxide, titanium oxide and Prussian blue and/or organic dyes such as alizarin dyes, azo dyes and metal phthalocyanine, and trace elements such as iron, manganese, boron, copper, cobalt, molybdenum and zinc.
  • inorganic pigments such as iron oxide, titanium oxide and Prussian blue
  • organic dyes such as alizarin dyes, azo dyes and metal phthalocyanine
  • trace elements such as iron, manganese, boron, copper, cobalt, molybdenum and zinc.
  • said additional components comprise herbicides selected from the group comprising acetochlor, acifluorfen, aclonifen, acrolein, AKH- 7088, alachlor, alloxydim, ametryn, amicarbazone, amidosulfuron, amitrole, ammonium sulfamate, anilofos, asulam, atrazine, azafenidin, azimsulfuron, BAS 625 H, beflubutamid, benazolin, benfluralin, benfuresate, bensulfuron-methyl, bensulide, bentazone, bifenox, bilanafos, bispyribac-sodium, borax, bromacil, bromobutide, bromoxynil, butachlor, butafenacil, butamifos, butralin, butroxydim, butylate, cafenstrole, carbetamide, carfentrazone
  • said additional components comprise insecticides selected from the group comprising 5-(2-chloropyrid-5-ylmethyl)-3-methyl-4- nitroiminoperhydro-l,3,5-oxadiazine, 5-(2-chlorothiazol-5-ylmethyl)-3-methyl-4- nitroiminoperhydro-l,3,5-oxadiazine, 3-methyl-4-nitroimino-5-(l-oxido-3- pyridinomethyl)perhydro-l,3,5-oxadiazine, 5-(2-chloro-l-oxido-5-pyridiniomethyl)- 3-methyl-4-nitroiminoperhydro-l,3,5-oxidiazine, 3-methyl-5-(2-methylpyrid-5- ylmethyl)-4-nitroiminoperhydro-l,3,5-oxadiazine, thiamethoxam (CAS RN 153719- 23-4), acetamiprid ((E)-N-[(6-chloropyr
  • said additional components comprise fungicides selected from the group comprising respiration inhibitors selected from the group comprising azoxystrobin, dimoxystrobin, enestroburin, fluoxastro-bin, kresoxim- methyl, meto-minostrobin, orysastrobin, picoxy-strobin, pyraclostrobin, pyrametostrobin, pyra oxyst robin, pyribencarb, trifloxystrobin, methyl(2-chloro-5 [1- (3-methylbenzyl-oxy-imino)-ethyl]benzyl)-carba-mate, 2 (2-(3-(2,6-di- chlorophenyl)-l-methyl-allylidene-aminooxy-methyl)-phenyl)-2-methoxyimino-N methyl-acetamide, famoxadone, fenamidone, benodanil, bixafen,
  • said additional components comprise agricultural adjuvants and/or carriers. More in particular, according to some embodiments, said additional components comprise liquid carriers, solid carriers, surface-active agents, or combinations thereof.
  • said liquid carriers are water and/or solvents selected from the group comprising toluene, xylene, petroleum naphtha, p-diethyl benzene, isopropyl benzene, m-xylene, o-xylene, p-xylene; cyclohexane, hexadecane, isooctane, n-hexane; paraffin oil, mineral oil, crop oil; chlorobenzene, 1,2-dichloropropane, 1.1.
  • -trichloroethane methylene chloride, trichloroethylene, perchloroethylene; alpha-pinene, d-limonene; lactic acid and ester derivatives, such as methyl lactate, ethyl lactate, butyl lactate, 2-ethylhexyl lactate; octadecanoic acid, oleic acid, propionic acid, xylene sulphonic acid and their ester forms; cyclohexanol, diacetone alcohol, diethylene glycol, dipropylene glycol, 2-ethyl hexanol, ethylene glycol, phenol, polyethylene glycol (PEG400), propylene glycol, triethylene glycol, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetra hydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol,
  • said solid carriers include talc, titanium dioxide, pyrophyllite clay, silica, kaolin clay, attapulgite clay, kieselguhr, chalk, diatomaceous earth, lime, montmorillonite clay, lime, calcium carbonate, bentonite clay, fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood floor, walnut shell flour, lignin, cellulose and the like.
  • surface-active agents are advantageously employed in the above- mentioned compositions, especially those designed to be diluted with carrier before application.
  • “Surface-active agents”, also known as surfactants, are compounds that lower the surface tension (or interfacial tension) between two liquids or between a liquid and a solid.
  • said surface-active agents are anionic, cationic, non-ionic or polymeric in character and may act as detergents, wetting agents, emulsifiers, foaming agents, and dispersants. Many organic compounds exhibit some surface-active properties; however specifically for the purposes of the invention nonionic surface-active agents can be used.
  • fatty alcohols such as cetyl alcohol, stearyl alcohol, and cetostearyl alcohol (consisting predominantly of cetyl and stearyl alcohols), and oleyl alcohol; but also polyethylene glycol alkyl ethers such as octaethylene glycol monododecyl ether and pentaethylene glycol monododecyl ether; polypropylene glycol alkyl ethers; polyethylene glycol - polypropylene glycol alkyl ethers; glucoside alkyl ethers such as decyl glucoside, lauryl glucoside or octyl glucoside; polyethylene glycol octylphenyl ethers; polyethylene glycol nonylphenyl ethers; polyethylene glycol tributylphenyl ethers; polyethylene glycol tristyryl phenyl ethers; polyethylene glycol - polypropylene glycol trist
  • said additional components comprise one or more compounds that function to improve crop plant compatibility, selected from the group comprising 4-dichloroacetyl-l-oxa-4-aza-spiro[4.5]-decane (AD-67, MON- 4660), l-dichloro-acetyl-hexahydro-3,3,8a-trimethylpyrrolo[l,2-a]-pyrimidin- 6(2H)-one (dicyclonon, BAS-145138), 4-dichloroacetyl-3,4-dihydro-3-methyl-2H- 1,4-benzoxazine (benoxacor), 1-methyl-hexyl 5-chloro-quinolin-8-oxy-acetate (cloquintocet-mexyl— cf.
  • AD-67, MON- 4660 4-dichloroacetyl-l-oxa-4-aza-spiro[4.5]-decane
  • EP-A-86750 also related compounds in EP-A-86750, EP-A-94349, EP-A- 191736, EP-A-492366), 3-(2-chloro-benzyl)-l-(l-methyl-l-phenyl-ethyl)-urea
  • 2-chloro-4-trifluoromethyl-thiazole-5-carboxylate (flurazole), 4-chloro-N-(l,3- dioxolan-2-yl-methoxy)-o-trifluoro acetophenone oxime (fluxofenim), 3- dichloroacetyl-5-(2-furanyl)-2,2-dimethyl-oxazolidine (furilazole, MON- 13900), ethyl 4,5-dihydro-5,5-diphenyl-3-isoxazolecarboxylate (isoxadifen-ethyl— cf.
  • EP-A-582198 4-carboxy- chroman-4-yl-acetic acid (AC-304415, cf. EP-A-613618), 4-chloro-phenoxy-acetic acid, 3,3'-dimethyl-4-methoxy-benzophenone, l-bromo-4-chloromethylsulphonyl- benzene, l-[4-(N-2-methoxybenzoylsulphamoyl)-phenyl]-3-methyl-urea (alias N- (2-methoxy-benzoyl)-4-[(methylamino-carbonyl)-amino]-benzenesulphonamide), l-[4-(N-2-methoxybenzoylsulphamoyl)-phenyl]-3,3-dimethyl-urea, l-[4-(N-4,5- dimethylbenzoylsulphamoyl)-phenyl]-3-methyl-urea, l-[
  • a second aspect of the present invention concerns a fungicide composition
  • a fungicide composition comprising valifenalate and cyazofamid, wherein said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1 :5.
  • compositions according to the second aspect of the invention are equally embodiments of the composition according to the second aspect of the invention.
  • preferred ranges, concentrations, and/or additional components of the composition used in the method according to the first aspect may be equally applicable to the composition of the second aspect.
  • the fungicide composition is for use in a method according to first aspect of the invention.
  • the composition of the invention may be applied as a tank mix comprising two or more tank mix parts.
  • a first tank mix part herein comprises at least said valifenalate and said cyazofamid, and a second tank mix part may comprise one or more additional components as described in any of the aforementioned embodiments.
  • composition of the invention may be applied as part of an application program, wherein a first application comprises applying at least said valifenalate and said cyazofamid.
  • a subsequent second, third or fourth application one or more additional components as described in any of the aforementioned embodiments may be applied.
  • a third aspect of the present invention concerns a method of improving plant resistance against pests and/or inducing plant defense pathways, said method comprising: providing a composition comprising valifenalate and cyazofamid, and applying said composition to a crop plant, a pest population associated with a crop plant, a habitat of a crop plant, or a combination thereof, characterized in that, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1 :5, and wherein said pest population comprises at least one organism chosen from the group of oomycetes.
  • plant resistance against pests refers to the inherent or induced ability of a plant to prevent, mitigate, or withstand damage caused by biotic stressors, such as insects, nematodes, fungi, bacteria, viruses, or other plant pests. This resistance may be achieved through various mechanisms, including but not limited to structural barriers, biochemical pathways, or genetic modifications. Structural barriers, such as waxy cuticles or trichomes, may physically deter pest infestation, while biochemical pathways may involve the production of secondary metabolites, proteins, or enzymes that are toxic or repellent to pests.
  • inducing plant defense pathways need be interpreted as activating or augmenting the plant's natural or engineered defense mechanisms in response to external stimuli, including pest attacks or environmental signals.
  • Such pathways may for example include the jasmonic acid (JA), salicylic acid (SA), or ethylene signaling pathways, which regulate the expression of defense-related genes.
  • Induction of these pathways may enhance the production of phytoalexins, pathogenesis-related (PR) proteins, or other antimicrobial compounds.
  • PR pathogenesis-related
  • Such induction may for example occur via external application of elicitors, such as chemical inducers, biological agents (e.g., beneficial microbes), or RNA-based technologies, or through environmental stimuli like mechanical damage or UV light exposure.
  • elicitors such as chemical inducers, biological agents (e.g., beneficial microbes), or RNA-based technologies, or through environmental stimuli like mechanical damage or UV light exposure.
  • These pathways may furthermore be harnessed or enhanced by genetic engineering, breeding strategies, or precision agriculture techniques
  • valifenalate and cyazofamid in the ratios as described herein allows that a target crop plant effectively obtains a better resistance against pest infestations and/or that plant defense pathways are induced in the target crop plant, which actively helps in fighting off pest infestations.
  • the herein described resistance and/or pathways provide an alternative or additional mode of action against pests, allowing the crop plant to better thrive in its habitat by preventing, mitigating or withstanding any possible damage or negative effects caused by pests.
  • improving plant resistance against pests and/or inducing plant defense pathways comprises inducing overexpression of one or more plant defense genes.
  • genes refers to the increased production or accumulation of a specific protein, polypeptide, or RNA molecule in a cell or organism, relative to its natural or basal expression levels.
  • plant defense genes need be interpreted as genes that encode proteins, peptides, metabolites, signaling molecules, or RNA molecules involved in recognizing, responding to, or mitigating biotic or abiotic stress. These genes may function directly by producing antimicrobial peptides, enzymes, structural proteins, or metabolites such as alkaloids or polyphenols; or indirectly by regulating signaling pathways that activate defense responses. Examples include genes encoding pathogenesis-related (PR) proteins, receptor-like kinases, and enzymes involved in the biosynthesis of secondary metabolites.
  • PR pathogenesis-related
  • improving plant resistance against pests and/or inducing plant defense pathways comprises inducing one or more plant defense pathways chosen from the group consisting of systemic acquired resistance pathways, in particular PR protein pathways, phenylpropanoid pathways, oxidative stress pathways, salicylic acid pathways, jasmonic acid pathways, or combinations thereof.
  • systemic acquired resistance (SAR) pathways refer to plant-wide defense mechanisms activated following localized exposure to a pathogen or stressor. SAR pathways involve the translocation of signaling molecules, such as salicylic acid or its derivatives, to uninfected parts of the plant, leading to the activation of defense-related genes. This response confers long-lasting and broadspectrum resistance against subsequent pathogen attacks.
  • SAR systemic acquired resistance
  • Pathways involving "pathogenesis-related (PR) proteins” encompass the biochemical and molecular processes by which plants produce PR proteins in response to biotic or abiotic stress. These proteins, such as chitinases, glucanases, and defensins, function as antimicrobial agents or regulators of the plant immune system. PR protein pathways are often activated by signaling molecules, including salicylic acid, and contribute to both local and systemic resistance mechanisms.
  • Phenylpropanoid pathways refer to a series of enzymatic reactions in plants that produce phenolic compounds derived from phenylalanine. These pathways play a critical role in plant defense by synthesizing secondary metabolites, such as lignins, flavonoids, and phytoalexins, which reinforce structural barriers, provide antioxidant properties, or exhibit antimicrobial activity. Key enzymes in this pathway include phenylalanine ammonia-lyase (PAL) and chaicone synthase (CHS).
  • PAL phenylalanine ammonia-lyase
  • CHS chaicone synthase
  • Oxidative stress pathways are cellular defense mechanisms activated in response to the accumulation of reactive oxygen species (ROS) caused by biotic or abiotic stress. These pathways regulate the production of antioxidant molecules and enzymes, such as catalases, peroxidases, and superoxide dismutases, to detoxify ROS and protect cellular components from oxidative damage. Oxidative stress pathways also serve as signaling mechanisms that activate broader defense responses.
  • ROS reactive oxygen species
  • Salicylic acid pathways are biochemical and molecular signaling cascades in plants that mediate defense responses to biotrophic pathogens and abiotic stress. These pathways regulate the activation of SAR, PR protein expression, and the production of antimicrobial metabolites. Salicylic acid acts as both a signaling molecule and a regulator of downstream defense genes involved in local and systemic resistance.
  • Jasmonic acid pathways are signaling pathways that mediate plant defense responses against herbivorous insects, necrotrophic pathogens, and mechanical damage. Jasmonic acid and its derivatives act as signaling molecules that activate genes involved in the synthesis of defensive compounds, such as proteinase inhibitors and secondary metabolites. These pathways interact with other hormonal signaling networks, including salicylic acid and ethylene, to fine-tune defense responses.
  • valifenalate and cyazofamid in the ratios as described herein allows that a target crop plant shows induction of the defense pathways described herein, which actively helps in fighting off pest infestations.
  • said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR5, PR8, PR14, PR15, PAL, CHS, DFR, ANS, PPO, HMGR, FPPS, Far, CSL, Apox, GST, POX, CalS, Peet, CAD, EDS1, WRKY, Lox2, JAR, ACCO, EIN3, or combinations thereof.
  • said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR5, PR8, PR14, PR15, or combinations thereof.
  • This group of plant defense genes preferably relates to the pathogenesis- related (PR) proteins pathway.
  • said plant defense genes are chosen from the group consisting of PAL, CHS, DFR, ANS, PPO, or combinations thereof.
  • This group of plant defense genes preferably relates to the phenylpropanoid pathways.
  • said plant defense genes are chosen from the group consisting of HMGR, FPPS, Far, or combinations thereof.
  • This group of plant defense genes preferably relates to the isoprenoid pathway.
  • said plant defense genes are chosen from the group consisting of Apox, GST, POX, or combinations thereof. This group of plant defense genes preferably relates to the antioxidant system pathway. According to a further or another embodiment, said plant defense genes are chosen from the group consisting of EDS1, WRKY, or combinations thereof. This group of plant defense genes preferably relates to the salicylic acid signaling pathway.
  • said plant defense genes are chosen from the group consisting of Lox2, JAR, or combinations thereof.
  • This group of plant defense genes preferably relates to the jasmonic acid signaling pathway.
  • said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR8, GST, POX, EDS1, WRKY, Lox2, or combinations thereof.
  • said method comprises observing a defense response lasting for at least 72 hours after applying said composition.
  • said method comprises inducing said plant defense pathways in the absence of pathogens or additional stimuli.
  • said pest population comprises at least one organism chosen from the group of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
  • said valifenalate and said cyazofamid are present in said composition according to a ratio of between 8: 1 and 1 :4.
  • said valifenalate and said cyazofamid are present in said composition according to a ratio of between 6: 1 and 1:3, more by preference of between 4: 1 and 1 :2, even more by preference of between 3: 1 and 1 : 1.
  • the method was found to be more effective in improving plant resistance against pests and/or inducing plant defense pathways.
  • said composition comprises from 10 to 50 wt.% of valifenalate, and from 5 to 25 wt.% of cyazofamid, based on the total weight of the composition.
  • compositions comprising from 10 to 50 wt.% of valifenalate and from 5 to 25 wt.% of cyazofamid demonstrated enhanced elicitor effects.
  • said composition comprises from 5 to 80 wt.% of valifenalate, based on the total weight of the composition.
  • said composition comprises from 10 to 60 wt.% of valifenalate, based on the total weight of the composition. More by preference, said composition comprises from 10 to 20 wt.% of valifenalate, based on the total weight of the composition.
  • said composition comprises from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition.
  • said composition comprises from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
  • said composition comprises from 5 to 80 wt.% of valifenalate, and from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 10 to 60 wt.% of valifenalate, and from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. Even more by preference, said composition comprises from 10 to 20 wt.% of valifenalate, and from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
  • said composition is formulated as a suspension concentrate (SC), an oil dispersion (OD), as a water dispersible granules (WG), as an emulsifiable concentrate (EC), as a concentrated oil-in-water emulsion (EW) as a wettable powder (WP), as a micro-emulsion (ME), as a capsule suspension (CS), as a suspoemulsion (SE), or as a mixed formulation of CS and SC (ZC).
  • SC suspension concentrate
  • OD oil dispersion
  • WG water dispersible granules
  • EW emulsifiable concentrate
  • EW concentrated oil-in-water emulsion
  • ME micro-emulsion
  • CS capsule suspension
  • SE suspoemulsion
  • ZC mixed formulation of CS and SC
  • composition is formulated as a suspension concentrate (SC).
  • applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha.
  • applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha. Most by preference, applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha. With increased preference, it has been shown that better balance is obtained between efficacy and crop safety.
  • applying said composition comprises applying cyazofamid in an amount of between 50 and 120 g Al/ha.
  • applying said composition comprises applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying cyazofamid in an amount of between 65 and 95 g Al/ha. Most by preference, applying said composition comprises applying cyazofamid in an amount of between 70 and 90 g Al/ha. With increased preference, it has been shown that more effective control is obtained with sustainable application rates, ensuring long-term crop protection and environmental safety.
  • applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha.
  • applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha, and applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha, and applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha, and applying cyazofamid in an amount of between 65 and 95 g Al/ha.
  • applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha, and applying cyazofamid in an amount of between 70 and 90 g Al/ha.
  • valifenalate in an amount of between 140 and 160 g Al/ha
  • cyazofamid in an amount of between 70 and 90 g Al/ha.
  • said crop plant is selected from the group of potato crops, tomato crops, (grape)vine crops, cucurbit crops, lettuce crops, ornamental plants, or combinations thereof.
  • Lettuce crops receive protection from Bremia lactucae, which causes downy mildew and can lead to severe crop losses.
  • the embodiment also covers ornamental plants, which are often affected by Peronospora sparsa and other oomycete pathogens, ensuring the health and aesthetic value of these plants in both commercial and domestic settings.
  • the ability to use this method across such a wide range of crops simplifies management strategies and enhances the overall efficacy of pest control.
  • said crop plant is selected from the group of potato crops.
  • said potato crop is chosen from the group of Solanum tuberosum, Solanum andigenum, Solanum phureja, Solanum stenotomum, Solanum ajanhuiri, or combinations thereof.
  • said crop plant is selected from the group of tomato crops.
  • said tomato crop is chosen from the group of Solanum lycopersicum, Solanum pimpinellifolium, Solanum cheesmaniae, Solanum peruvianum, Solanum habrochaites, or combinations thereof.
  • said crop plant is selected from the group of (grape)vine crops.
  • said (grape)vine crop is chosen from the group of Vitis vinifera, Vitis labrusca, Vitis riparia, Vitis rotundifolia, Vitis amurensis, or combinations thereof.
  • said crop plant is selected from the group of cucurbit crops.
  • said cucurbit crop is chosen from the group ofCucumis sativus, Cucumis melo, Cucurbita pepo, Cucurbita maxima, Cucurbita moschata, Citrullus lanatus, or combinations thereof.
  • said crop plant is selected from the group of lettuce crops.
  • said lettuce crop is chosen from the group of Lactuca sativa, Lactuca sativa var. longifolia, Lactuca sativa var. crispa, Lactuca sativa var. capitata, Lactuca sativa var. angustana, or combinations thereof.
  • said crop plant is selected from the group of ornamental plants.
  • said ornamental plant is chosen from the group of Rosa spp., Chrysanthemum spp., Pelargonium spp., Petunia spp., Impatiens spp., Begonia spp., or combinations thereof.
  • composition according to the second aspect is used in a method according to the third aspect of the invention.
  • Example 1 Controlling Phytophthora infestans in potato according to some embodiments of the invention.
  • Potato crop plants were infected with CAA resistant genotype EU43_A1.
  • Pre-germinated potato tubers (“Bintje” cultivar) were planted in 500 mL pots and stored in greenhouse conditions to grow. A first treatment was performed as soon as the crop plants were 20 to 25 cm tall.
  • the crop plants were treated with a boom sprayer in the greenhouse, with a water volume of 200 L/ha.
  • the treatments, in particular their composition and application dosage, are summarized in Table 2.
  • each pot was scored as a whole for % disease severity, for example by rating the pot in relation to the appropriate % disease category described below in terms of average numbers of spots per plant, number of leaflets attacked, the form of the plants and the general appearance of the pot.
  • Percent disease severity is defined as follows:
  • Efficacy (%) (severityuTc - severitytreatment) I (severityuTc) x 100 and synergistic effect was calculated according to the Colby formula as described, wherein results lower or higher than 1 show antagonism or synergism respectively.
  • Example 1 The test results of Example 1 are shown in Table 3. Table 3. Test results regarding the control of Phytophthora infestans (genotype EU43_A1, CAA resistant) in potato according to some embodiments of the invention.
  • Example 2 Controlling Plasmopara viticola in grapevines according to some embodiments of the invention.
  • Treatments were duplicated to infect with 2 strains of Plasmopara viticola, consisting of a CAA sensitive strain (A) and a CAA resistant strain (B), in particular resistance to valifenalate.
  • A CAA sensitive strain
  • B CAA resistant strain
  • strains were multiplied on untreated leaves of 8 days before infection in order to produce enough inoculum to a correct contamination. During these replication steps and before the trial, the sensitivity to the valifenalate was evaluated to validate the sensitivity profile of the strain. Genetic analysis was also carried out to confirm the resistant and sensitive profile of these strains. Half of the crop plants were infected with strain A, while the other half of the crop plants were infected with strain B.
  • the tests were carried out on young Cabernet sauvignon plants. They were produced in a greenhouse, in a temperature of between 18 and 30 °C from one-eye shoots. These plants were grown in a greenhouse under conditions that ensure control of the quality of the plants and their health status during their cultivation. Homogeneous sets of 6 plants were constituted for the study of each trial condition. A total of 60 plants was required to study all the conditions.
  • application mode was a spraying of fungicide on whole plant. Both upper and lower surfaces of the leaves were treated.
  • a classical application method by spraying was used: the plants were placed in a spray booth equipped with a spray bench carrying 5 nozzles (2 lateral right, 2 lateral left and 1 upper). This bench moves on a guidance rail at a constant speed. The spraying begins from the moment is initiated and before to reach the first plant in order to treat all plants of the same set simultaneously and homogeneously.
  • the pressure at which spraying is applied and the speed of the bench are a function of the volume to be supplied. In this example, the volume of water used was 600 L/ha.
  • the treatments, in particular their composition and application dosage, are summarized in Table 4.
  • the suspensions of sporocystes of Plasmopara viticola were prepared by washing infected leaves with demineralized water at low temperature in order to block the release of zoospores. The sporulations of the fungus were thus harvested and the spore suspension was then titrated with a Malassez cell. The optimal concentration is 50000 spores/mL.
  • Two suspensions of sporocystes were prepared, on one hand, a suspension with the sensitive strain and, on the other hand, a suspension with the resistant strain. The plants were inoculated by spraying a sporangial suspension on the lower surface of the leaves. Each plant was treated separately and contaminated on each leaf stage. On average, 10 mL was necessary for the contamination of 6 levels of leaves.
  • the plants were gathered (separating CAA sensitive and CAA resistant inoculated plants) inside a hermetic enclosure so as to maintain a saturated relative humidity, necessary for the development of the disease.
  • Conditions were as follows: a temperature of between 21 and 22 °C, a humidity of 100 %, and a light/dark schedule of 14h/10h lig ht/dark during 8 consecutive days. At the end of this incubation period, the severity of the disease was assessed on each plant and on leaves.
  • Example 2 The test results of Example 2 are shown in Tables 5 and 6. Table 5. Test results regarding the control of Plasmopara viticola (strain A, CAA sensitive) in grapevine according to some embodiments of the invention.
  • compositions were sprayed on potato leaves carried out up to the runoff limit at the 4th leaf stage. Compositions were applied twice, 4 days apart, in order to maximize the potential expression of defense genes. The dose of the different compositions are presented in Tables 7 and 8.
  • Samples were taken on leaves from three plants of three pots, and bulked in a tube for analysis (technical replicates). For each date, samples were taken from different plants. Samples were collected at 24 hours (24H) and 72 hours (72H), and right after treatments (DO). Analysis tubes with root samples were immediately immerged in liquid nitrogen after sampling to prevent RIMA degradation and then kept at -80°C before processing.
  • RNAs were extracted using the Macherey Nagel Nucleospin® RNA Plant Kit and a DNAse treatment was performed during extraction, according to the supplier's instructions. For each sample, an RNA quantification and quality control was performed. A reverse transcription (RT) step was then performed on the standardized RNAs.
  • RT reverse transcription
  • the qPFD® microarray (WO/2011/161388, Brisset MN, INRA IRHS) is a molecular diagnostic tool measuring the level of expression of plant defense genes by qPCR (Quantitative Polymerase Chain Reaction) at a given time.
  • the targeted genes are involved in defense mechanisms of the following three main classes: chemical barriers, physical barriers and hormonal signaling.
  • the level of expression of these genes provides information on the state of stimulation of the defenses of the plants analyzed.
  • Each sample was analyzed using 24 defense genes and 3 reference genes (TuA, Actin, GAPDH) of the qPFD® microarray.
  • the results of the qPFD® were evaluated according to the 2-AACT method which provides the relative expressions of the defense genes in a given sample compared to a control sample (calibrator), expressions normalized by the geometric mean of the 3 reference genes (TuA, Actin, GAPDH) of this sample.
  • the gene expression profiles are visualized in the form of a density map, called Heatmap.
  • treatment 4 according to the invention exhibited the strongest defense-stimulating effect, eliciting 8 genes on different defense pathways (PR protein pathway, phenylpropanoid pathway, oxidative stress pathway, salicylic acid pathway and jasmonic acid pathway). Treatments 2, 3 and 5 had little or no effect on the defense genes tested at 72h. Trial 2
  • Treatment 3 (tank mix of valifenalate and cyazofamid), a significant PDS effect was observed 24h after treatment, for 4 genes. But no PDS effect was observed 72h after treatment.
  • Treatment 4 composition comprising valifenalate and cyazofamid according to the invention shows a higher PDS effect, with a larger number of genes (9 genes) 24 after treatment and still 3 genes 72h after treatment.

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Abstract

The invention relates to a method of controlling pests, said method comprising: providing a composition comprising valifenalate and cyazofamid, and applying said composition to a crop plant, a pest population associated with a crop plant, a habitat of a crop plant, or a combination thereof, wherein said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10:1 and 10 1:5, and wherein said pest population comprises at least one organism chosen from the group of oomycetes. The present invention also concerns a method of improving plant resistance against pests and/or inducing plant defense pathways.

Description

METHOD OF CONTROLLING PESTS WITH A COMPOSITION COMPRISING
VALIFENALATE AND CYAZOFAMID
TECHNICAL FIELD
The invention relates to a method of improving plant resistance against pests and/or inducing plant defense pathways with a composition comprising valifenalate and cyazofamid. More in particular, the invention relates to a method of controlling carboxylic acid amide (CAA) resistant pests.
BACKGROUND
In crop protection, it is in principle desirable to increase the specific action of a pesticidal active substance and the safety of operation. The pesticidal activity of many pesticides is already on a high level, but generally depends on the application rate, the respective preparation form, the respective pests to be controlled, the climatic and soil conditions, etc. Thus, there is frequently a need for targeted synergistic activity against specific species of pests, control of pests with better overall selectivity, generally lower amounts of active compounds used for equally good control results, and for a reduced active compound input into the environment to avoid, for example, leaching and carry-over effects. However, in the combined use of a plurality of active compounds, there are frequently phenomena of chemical, physical, or biological incompatibility, such as decomposition of an active compound or antagonism in the biological activity of the active compounds.
In modern agriculture, the management of plant diseases caused by oomycetes, such as late blight, downy mildew, and root rot, is critical for ensuring high crop yields and quality. Oomycetes, which include notorious genera such as Phytophthora, Plasmopara, and Pseudoperonospora, are responsible for significant economic losses globally due to their ability to rapidly infect and devastate a wide variety of crops. Traditional methods for controlling these pathogens include cultural practices, resistant cultivars, and the application of chemical fungicides.
Among chemical fungicides, carboxylic acid amides (CAA) have been widely used due to their effectiveness in inhibiting the biosynthesis of cell walls in oomycetes. However, the extensive use of CAA fungicides has led to the emergence of resistant strains, posing a significant challenge to disease management. This resistance necessitates the development of new strategies and formulations that can effectively control both sensitive and resistant strains of oomycetes.
One promising approach is the use of combination fungicides that incorporate multiple active ingredients with different modes of action. Most combinations may however lead to worse results, in particular an antagonistic effect may be observed in some combinations. Formulation technologies may also play a crucial role in optimizing the performance of these combination fungicides.
The present invention aims to resolve at least some of the problems mentioned above. It is furthermore an object of the present invention to provide pesticide compositions as alternatives to the prior art, or as improvements thereof.
SUMMARY OF THE INVENTION
A first aspect of the present invention provides a method of controlling pests according to claim 1.
The method of the first aspect was found to be effective in controlling at least one organism chosen from the group of oomycetes, and showed consistent results over a broad range of organisms within this group. The management of oomycete infections is particularly challenging, partly due to their ability to develop resistance to certain classes of pesticides, such as carboxylic acid amides (CAA). Resistances can generally lead to reduced efficacy of the pesticide, necessitating higher doses or more frequent applications, and often prompting the use of alternative or combination treatments to manage resistant strains effectively. The method of the invention unexpectedly showed improved efficacy without needing to increase dosage or application rates and was able to effectively combat a broad range of oomycetes.
Further aspects of the invention relate to a method of improving plant resistance against pests and/or inducing plant defense pathways according to claim 14, and to a fungicidal composition according to claim 27.
The method according to the third aspect of the invention allows that a target crop plant effectively obtains a better resistance against pest infestations and/or that plant defense pathways are induced in the target crop plant, which actively helps in fighting off pest infestations. The herein described resistance and/or pathways provide an alternative or additional mode of action against pests, allowing the crop plant to better thrive in its habitat by preventing, mitigating or withstanding any possible damage or negative effects caused by pests.
DETAILED DESCRIPTION OF THE INVENTION
The present invention concerns a method of controlling pests with a composition comprising valifenalate and cyazofamid.
Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.
As used herein, the following terms have the following meanings:
"A", "an", and "the" as used herein refers to both singular and plural referents unless the context clearly dictates otherwise. By way of example, "a compartment" refers to one or more than one compartment.
"Comprise", "comprising", and "comprises" and "comprised of" as used herein are synonymous with "include", "including", "includes" or "contain", "containing", "contains" and are inclusive or open-ended terms that specifies the presence of what follows e.g. component and do not exclude or preclude the presence of additional, non-recited components, features, element, members, steps, known in the art or disclosed therein.
The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within that range, as well as the recited endpoints.
The expression "% by weight", "weight percent", "%wt" or "wt.%", here and throughout the description unless otherwise defined, refers to the relative weight of the respective component based on the overall weight of the formulation. Whereas the terms "one or more" or "at least one", such as one or more or at least one member(s) of a group of members, is clear per se, by means of further exemplification, the term encompasses inter alia a reference to any one of said members, or to any two or more of said members, such as, e.g., any >3, >4, >5, >6 or >7 etc. of said members, and up to all said members.
Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, definitions for the terms used in the description are included to better appreciate the teaching of the present invention. The terms or definitions used herein are provided solely to aid in the understanding of the invention.
Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art.
A first aspect of the present invention relates to a method of controlling pests, said method comprising: providing a composition comprising valifenalate and cyazofamid, and applying said composition to a crop plant, a pest population associated with a crop plant, a habitat of a crop plant, or a combination thereof, wherein said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1:5, and wherein said pest population comprises at least one organism chosen from the group of oomycetes.
In light of the present invention, the term "pest" is to be interpreted as any organism, typically an insect, mite, nematode, weed, fungus, bacterium, virus, or other microorganism, that negatively impacts human activities by damaging crops, livestock, property, or causing harm to health. In the context of agriculture, pests are organisms that directly or indirectly harm crops by feeding on plant tissues, transmitting diseases, or competing with crops for nutrients, water, and light. Pests can cause significant economic losses by reducing crop yields, affecting the quality of produce, and increasing production costs due to the need for pest management practices. Effective pest control generally involves integrated pest management (IPM) strategies that combine biological, chemical, cultural, and mechanical methods to minimize pest populations and their impact while promoting sustainable agricultural practices. The pests according to the method of the invention are preferably organisms chosen from the class of oomycetes.
The terminology "crop plant", need to be understood as any plant species that is cultivated intentionally for the purpose of harvesting a product of economic value. Crop plants are grown extensively in agriculture for various uses, including food (such as cereals, fruits, vegetables), feed (for livestock), fiber (such as cotton, hemp), oil (such as soybeans, sunflower), biomass (for biofuel production), medicinal substances (such as herbs, pharmaceuticals), and ornamental purposes. Crop plants are selected based on their suitability to specific climatic, soil, and environmental conditions, and they are managed through agricultural practices such as planting, irrigation, fertilization, pest control, and harvesting to optimize growth and yield. The choice of crop plant may be influenced by market demand, economic considerations, and the adaptability of the plant to local growing conditions.
When referring to a "habitat of a crop plant", the specific environment or area where the crop plant is grown and cultivated is intended. This habitat includes various physical, chemical, and biological factors that influence the growth, development, and productivity of the crop. Key components of the habitat of a crop plant may include soil type (texture, structure, fertility, pH), climate (temperature, precipitation, humidity, sunlight), water availability (irrigation practices, rainfall), and the presence of other organisms (beneficial insects, pests, weeds, microorganisms). The habitat may also encompass the agricultural practices and management techniques employed by farmers to create optimal growing conditions for the crop. Understanding the habitat of a crop plant is important for making informed decisions about crop selection, planting schedules, pest and disease management, and sustainable farming practices to ensure high yields and quality produce. In light of the present invention, the term "valifenalate" is directed to a carboxylic acid amide (CAA) fungicide. It mainly functions by inhibiting the cellulose synthase enzyme, which is crucial for the cell wall synthesis in some organisms, such as oomycetes. This inhibition disrupts the formation of the cell wall, leading to the death of the cell. Valifenalate has been used against oomycete pathogens in various crops, including grapes, potatoes, and tomatoes. It is known for its systemic action, allowing it to be absorbed and translocated within the plant, providing protection to new growth. The chemical structure of valifenalate can be represented by its IUPAC name: 2-(2-(l-(4-chlorophenyl)-3-(4-methylphenyl)ureido)-3,3-dimethylbutan- amido)-2-methylpropanoic acid methyl ester.
The term "cyazofamid" refers to a fungicide belonging to the cyano-imidazole chemical group. It mainly acts by inhibiting complex III (cytochrome bcl complex) in the mitochondrial electron transport chain of oomycetes, thereby disrupting cellular respiration and energy production. This mode of action is effective against a wide range of oomycete diseases, including downy mildew and late blight. Cyazofamid is known for its protective and curative properties, making it a valuable component in various integrated pest management programs. The chemical structure of cyazofamid is denoted by its IUPAC name: 4-chloro-2-cyano-N,N- dimethyl-5-(4-methylphenyl)-lH-imidazole-l-sulfonamide.
When referring to "oomycetes", also known as water molds, a distinct group of fungus-like organisms classified under the kingdom Stramenopiles is intended. They are characterized by their filamentous, coenocytic hyphae and cell walls made of cellulose rather than chitin, which distinguishes them from true fungi. Oomycetes include many plant pathogenic species, such as those causing downy mildew and root rot. Notable genera include Phytophthora, Plasmopara, Pythium, and Aphanomyces. These pathogens are notorious for causing severe agricultural losses due to their ability to rapidly spread and infect a wide range of host plants. In light of the invention, the "group of oomycetes" may also be referred to as the "class of oomycetes". By preference, said pest population thus comprises at least one organism chosen from the class of oomycetes.
The method of the invention was found to be effective in controlling at least one organism chosen from the group of oomycetes, and showed consistent results over a broad range of organisms within this group. The management of oomycete infections is particularly challenging, partly due to their ability to develop resistance to certain classes of pesticides, such as carboxylic acid amides (CAA). Resistances can generally lead to reduced efficacy of the pesticide, necessitating higher doses or more frequent applications, and often prompting the use of alternative or combination treatments to manage resistant strains effectively. The method of the invention unexpectedly showed improved efficacy without needing to increase dosage or application rates and was able to effectively combat a broad range of oomycetes.
In light of the invention, the wording "synergistically effective" may be used, which refers to a combination of two or more substances which, when used together, produce a greater effect than the sum of their individual effects. This synergism implies that the combined action of these substances is more effective at controlling pests than when they are used separately. The Colby calculation is often used to quantify this synergy. It is a mathematical formula that predicts the expected effectiveness of a combination of substances based on their individual efficacies.
A synergistic effect in pesticides is always present when the pesticide action of the active compound combination exceeds the action of the active compounds when applied individually.
The expected activity of a given combination of pesticides A and B can be calculated as follows according to a calculation method by Colby (cf. COLBY, S. R.: "Calculating synergistic and antagonistic responses of herbicide combinations", Weeds 15, pages 20-22, 1967), the equation reading:
E = X + Y - (X x Y) / 100 wherein:
X is the amount of damage (expressed in %) done by pesticide A at an application rate of m g/ha,
Y is the amount of damage (expressed in %) done by pesticide B at an application rate of n g/ha, and
E is the expected amount of damage (expressed in %) done by the combination of pesticides A and B at their respective application rates of m and n g/ha. The wording "amount of damage" may in the light of the present invention also be read as "amount of disease control" or "amount of efficacy", which alternative wordings may read more appropriately in the context of fungicidal activity. Similarly in this context, the wording "damage" may also be read as "disease control" or "efficacy".
If the actual damage exceeds the calculated value (E), the activity of the combination is super additive, i.e. it shows a synergistic effect. In this case, the damage actually observed must exceed the values calculated using the above formulae for the expected damage E.
The Colby calculation can be similarly used to indicate an "antagonistic effect", or to indicate a merely "additive effect" between compounds. In case the actual damage is lower than the calculated value (E), the activity of the combination is antagonistic. In case the actual damage equals the calculated value (E), the activity of the combination is merely additive.
It is noted that while Colby is often formulated for herbicides, its general teachings may extend to all kinds of pesticides.
In light of the invention, it was now found that carboxylic acid amide (CAA) fungicides and fungicides belonging to the cyano-imidazole chemical group in some instances may exhibit an antagonistic effect when used in combination. Hence when controlling pests, the required dosages or application rates of carboxylic acid amide (CAA) fungicides and fungicides belonging to the cyano-imidazole chemical group may need to be increased in order to provide adequate or effective control.
According to some embodiments, it was now unexpectedly found that the combination of valifenalate and cyazofamid in the ratios as described herein allowed to reduce the antagonistic effect which is commonly observed. By preference, the antagonistic effect is reduced by at least 1 %. More by preference, the antagonistic effect is reduced by at least 2 %, at least 3 %, at least 4 %, or at least 5 %. Even more by preference, the antagonistic effect is reduced by at least 10 %, at least 15 %, or at least 20 %.
Even more by preference, the combination of valifenalate and cyazofamid in the ratios as described herein allowed to reach an "additive effect". Even more by preference, the combination of valifenalate and cyazofamid in the ratios as described herein allowed to reach a "synergistic effect".
The method of the invention thus unexpectedly showed improved efficacy without needing to increase dosage or application rates and was able to effectively combat a broad range of oomycetes.
According to a further or another embodiment, said pest population comprises at least one organism chosen from the group of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
The term "Phytophthora" relates to a genus within the oomycetes, encompassing several species known for their negative impact on agriculture. Species like Phytophthora infestans, for example, cause late blight in potatoes and tomatoes, while Phytophthora capsici may affect peppers and cucurbits. These pathogens mostly thrive in moist environments and are characterized by their production of sporangia and zoospores, which facilitate rapid dissemination. Control of Phytophthora is challenging due to their resilience and ability to survive in soil and plant debris for extended periods of time.
"Plasmopara" is a genus of oomycetes responsible for downy mildew diseases, for example in grapevines Plasmopara viticola). These pathogens generally infect the aerial parts of plants, causing characteristic symptoms such as yellowing, chlorosis, and downy white growth on the undersides of leaves. Plasmopara species produce sporangia that are spread by wind and water, leading to new infections. Common practices of managing Plasmopara may involve the use of fungicides, resistant cultivars, and cultural practices to reduce humidity and leaf wetness.
In light of the present invention, the wording "Bremia" need to be understood as a genus of oomycetes that primarily affects lettuce and other leafy vegetables, for example causing downy mildew (Bremia lactucae). This pathogen generally thrives in cool, humid conditions and can cause significant crop losses by reducing photosynthesis and promoting secondary infections. Bremia produces sporangia on sporangiophores, which emerge from stomata on the undersides of leaves, giving a white, downy appearance. Common control strategies for Bremia include the use of fungicides, resistant varieties, and environmental management to minimize leaf wetness. "Pseudoperonospora" is a genus of oomycetes that includes species such as Pseudoperonospora cubensis, the causative agent of downy mildew in cucurbits. This pathogen is highly destructive and can rapidly defoliate plants, leading to reduced yields and fruit quality. Pseudoperonospora produces sporangia that are dispersed by wind and rain, facilitating widespread infection. Common management practices involve the application of fungicides, crop rotation, and the use of resistant cultivars.
"Peronospora" is a genus of oomycetes known for causing downy mildew diseases in a variety of host plants, including ornamentals, vegetables, and legumes. Species like Peronospora farinosa affect spinach, while Peronospora sparsa infects roses. These pathogens produce sporangia on the surface of infected plant tissues, leading to a characteristic downy appearance. Control of Peronospora commonly involves the use of fungicides, resistant plant varieties, and cultural practices to reduce the incidence of infection.
The method as described herein effectively allows to control each of the discussed oomycetes genera, preferably by implementing less complex control strategies than those know in the art. It was observed that the method improved efficacy without needing to increase dosage or application rates, and was able to effectively combat several genera within the group of oomycetes that are notorious for being the most difficult to control.
In light of the above, considering that the aforementioned group consists of several genera, by preference, said pest population thus comprises at least one organism chosen from the genus of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
According to some embodiments, said pest population comprises at least one organism chosen from the group of Phytophthora infestans, Phytophthora capsica, Phytophthora sojae, Phytophthora ramorum, Phytophthora cinnamon, Plasmopara viticola, Bremia lactucae, Pseudoperonospara cubensis, Peronospora farinose, Peronospora sparsa, or combinations thereof.
"Phytophthora infestans" is a highly destructive oomycete pathogen responsible for late blight in potatoes and tomatoes, among other crops. It is characterized by its ability to cause rapid and severe foliar blight, stem lesions, and tuber rot, leading to significant yield losses. The pathogen thrives in cool, moist conditions and can spread quickly via wind-dispersed sporangia. Common control measures include the use of resistant cultivars, fungicides, and cultural practices to reduce moisture on plant surfaces.
"Phytophthora capsica" is an aggressive pathogen that causes root, crown, and fruit rot in a wide range of vegetable crops, including peppers, cucurbits, and tomatoes. This oomycete thrives in warm, wet environments and can survive in soil and plant debris for extended periods. Infected plants exhibit symptoms such as wilting, stunted growth, and fruit rot. Common management strategies include crop rotation, the use of resistant varieties, soil drainage improvement, and fungicide applications.
"Phytophthora sojae" is an oomycete responsible for causing Phytophthora root and stem rot in soybeans. This pathogen infects soybean plants at all growth stages, leading to damping-off, root rot, stem cankers, and ultimately plant death. Phytophthora sojae thrives in waterlogged soils and spreads through soil and water. Common control involves using resistant soybean cultivars, improving soil drainage, and applying fungicides where resistance management practices are necessary.
"Phytophthora ramorum" is the causal agent of sudden oak death and ramorum blight, affecting a variety of trees and ornamental plants. This pathogen is notorious for causing extensive mortality in oak and tanoak trees, which are prevalent in North America. Symptoms include leaf spots, shoot dieback, and bark cankers that exude a dark, sticky sap. Phytophthora ramorum spreads through infected plant material, soil, and water. Common control measures include sanitation practices, removal of infected plants, and regulatory quarantine to prevent spread.
Phytophthora cinnamomi is a soil-borne oomycete that causes root rot in a very broad range of plant species, including many agricultural and horticultural crops. It leads to root necrosis, reduced water and nutrient uptake, wilting, and plant death. This pathogen is particularly destructive in avocado, chestnut, and eucalyptus plantations. Common control methods include improving soil drainage, applying fungicides, and using resistant rootstocks.
"Plasmopara viticola" is an oomycete responsible for downy mildew in grapevines. It causes yellowish, oily spots on the upper leaf surface and white, downy growth on the underside. Severe infections can lead to defoliation, reduced photosynthesis, and poor fruit quality. Plasmopara viticola generally thrives in warm, humid conditions and spreads through sporangia dispersed by wind and rain. Common management includes fungicide applications, canopy management to improve air circulation, and the use of resistant grape varieties.
"Bremia lactucae" is an oomycete that causes downy mildew in lettuce. Infected plants exhibit yellowing and chlorosis of leaves, along with white, downy fungal growth on the undersides. This pathogen can cause significant crop losses in both field and greenhouse environments. Bremia lactucae mainly spreads through airborne sporangia and requires cool, humid conditions for infection. Control measures include resistant cultivars, fungicides, and environmental management to reduce leaf wetness.
"Pseudoperonospora cubensis" is an oomycete responsible for downy mildew in cucurbits, including cucumbers, melons, and squash. Symptoms include angular, yellow lesions on leaves that become necrotic, leading to defoliation and reduced yield. The pathogen spreads through wind-dispersed sporangia and thrives in warm, humid conditions. Management strategies include fungicide applications, resistant varieties, and crop rotation to reduce inoculum levels.
"Peronospora farinosa" is an oomycete that causes downy mildew in spinach and other leafy vegetables. Infected plants display yellowing, chlorosis, and a grayish, downy growth on the undersides of leaves. This pathogen mainly spreads through wind-borne spores and requires cool, moist conditions for infection. Control measures include using resistant cultivars, applying fungicides, and practicing good field sanitation.
"Peronospora sparsa" is an oomycete responsible for downy mildew in roses and other ornamentals. Symptoms include yellowing and spotting on leaves, with a white to grayish fungal growth on the undersides. This pathogen commonly spreads through airborne sporangia and thrives in cool, moist environments. Common management includes fungicide applications, removing infected plant material, and ensuring good air circulation around plants.
The method as described herein allows to effectively control each of the aforementioned oomycetes in a very wide range of crops. Efficacy was found to be consistently high, especially in comparison to management strategies making use of fungicide components as known in the art. The method thus allows to significantly reduce the complexity of existing pest management strategies.
In light of the above, considering that the aforementioned group consists of several species, by preference, said pest population thus comprises at least one organism chosen from the species of Phytophthora infestans, Phytophthora capsica, Phytophthora sojae, Phytophthora ramorum, Phytophthora cinnamon, Plasmopara viticola, Bremia lactucae, Pseudoperonospara cubensis, Peronospora farinose, Peronospora sparsa, or combinations thereof.
According to a further or another embodiment, said pest population comprises at least one strain which is carboxylic acid amide (CAA) resistant.
In light of the invention "carboxylic acid amide (CAA) resistant" organisms relate to those organisms that have developed resistance to fungicides within the CAA class, such as valifenalate and dimethomorph. Resistance is often due to genetic mutations that alter the target site of the fungicide, reducing its efficacy. These resistant organisms can thus better survive and proliferate despite fungicide applications, making disease management more difficult. In current practices, monitoring for resistance and using integrated pest management strategies are essential to mitigate the impact of CAA resistance.
The method as described herein was found to be surprisingly effective in controlling a wide variety of oomycetes, even those that have developed CAA resistance. Not only does this allow to improve controlling CAA resistant organisms, it also means that the method can be used in management strategies targeting a broad scope of oomycetes. Therefore, management strategies may be significantly simplified and the herein described method may be effectively applicable to most infestations of oomycetes.
According to a further or another embodiment, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 1,1.
The term "resistance factor (RF)", in light of the invention towards at least one carboxylic acid amide (CAA), refers to a quantitative measure of the degree of resistance that a pest population has developed, particularly a quantitative measure of the degree of resistance that oomycetes have developed against fungicides in the carboxylic acid amide class. The resistance factor is calculated in laboratory assay by comparing the effective concentration (ECso) of a pesticide, which is the concentration required to inhibit 50 % of the pest population, in a resistant strain to the EC50 required for a sensitive, non-resistant strain. Mathematically, this may be expressed as:
Resistance factor (RF) = EC50 of resistant strain I EC50 of non-resistant strain.
An RF value of 1 indicates no resistance, meaning the fungicide is equally effective against both strains. Higher RF values indicate a greater degree of resistance, with an RF value of 10 meaning that the resistant strain requires ten times the concentration of the fungicide to achieve the same level of control as the sensitive strain. This metric is crucial for understanding the extent of fungicide resistance in pest populations and for developing effective resistance management strategies.
As the resistance factor (RF) is determined under laboratory conditions, the pest populations referred to herein are assessed in the form of pest isolates. In particular, the resistant pest population is represented by an isolate of a resistant strain, while the non-resistant pest population is represented by an isolate of a non-resistant strain.
Preferably, the non-resistant pest population is represented by a plurality of isolates of non-resistant strains. This approach allows for the determination of a baseline resistance factor (RF) for the non-resistant population. More preferably, the non- resistant pest population is represented by at least 20 isolates of non-resistant strains. Even more preferably, the non-resistant pest population is represented by at least 30, 40, 50, 60, 70, 80, 90, 100, 125, or even 150 isolates of non-resistant strains.
The method as described herein was found to be surprisingly effective in controlling a wide variety of oomycetes, including those with a resistance factor (RF) of at least 1,1 towards carboxylic acid amides (CAA). This indicates that the method significantly enhances control over CAA-resistant organisms, thereby enabling its use in comprehensive management strategies targeting a broad spectrum of oomycetes. As a result, there is no need to modify the strategy based on the presence or absence of CAA resistance, simplifying management practices. Consequently, the described method can be effectively applied to most oomycete infestations, providing a robust and versatile solution for pest control.
By preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 1,2, more by preference of at least 1,3, 1,4, or 1,5. Even more by preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 2, 3, 4, 5, 6, 7, 8, or 9,0. Even more by preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 10. Even more by preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.
From a practical perspective, in certain embodiments, the non-resistant pest population is represented by a plurality of isolates of non-resistant strains, wherein the determined baseline resistance factor (RF) exhibits a variance within a predefined range, preferably a predefined range of [-10; + 10], [-20;+20], [- 30; + 30], [-40;+40], or even [-50; + 50].
Even more by preference, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 50, 100, 250, 500, 1000, 5000, 10000, 20000, 30000, or 40000, or even 50000.
According to a further or another embodiment, said pest population having a resistance factor according to any of the foregoing embodiments, is a pest isolate.
According to a further or another embodiment, said carboxylic acid amide (CAA) fungicide is chosen from the group of valifenalate, dimethomorph, flumorph, pyrimorph, benthiavalicarb, iprovalicarb, mandipropamid, or combinations thereof.
In light of the invention, "dimethomorph" is a systemic fungicide belonging to the carboxylic acid amide (CAA) class, used primarily to control oomycete pathogens such as downy mildew and late blight. It acts by inhibiting the biosynthesis of sterols in the cell membranes of fungi, disrupting cell wall formation and leading to the death of the pathogen. Dimethomorph is used both as a preventative and curative treatment, with good translaminar and systemic movement within the plant. The chemical structure of dimethomorph can be represented by its IUPAC name: (E,Z)- 4-(3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)acryloyl)morpholine.
"Flumorph" is a fungicide used to control oomycetes, particularly in crops such as potatoes, tomatoes, and grapes. It generally works by disrupting the formation of the fungal cell wall, thereby inhibiting the growth and spread of the pathogen. Flumorph is known for its protective action, making it effective when applied before the onset of disease. Its chemical structure can be denoted by its IUPAC name: 3- (3,5-dichlorophenyl)-2-methoxy-4-(trifluoromethyl)phenyl methanesulfonate.
"Pyrimorph" is a fungicide that belongs to the CAA class and is used to control a variety of oomycete pathogens, including Phytophthora infestans, which causes late blight in potatoes and tomatoes. It acts by inhibiting the synthesis of cell wall components in the pathogens, thereby preventing their growth and reproduction. Pyrimorph is used both as a curative and preventive treatment. The chemical structure of pyrimorph is represented by its IUPAC name: 4-(2-chlorobenzyl)-N- (l,l-dimethyl-2-propynyl)-pyrimidin-5-amine.
In light of the present invention "benthiavalicarb" is to be read as a fungicide used to control oomycete diseases such as downy mildew and late blight in various crops. It belongs to the carboxylic acid amide (CAA) class and works by inhibiting the biosynthesis of cellulose in the cell walls of the pathogens, leading to their death. Benthiavalicarb is known for its systemic properties, providing both protective and curative effects. The chemical structure of benthiavalicarb can be described by its IUPAC name: (RS)-2-(l-{[l-(4-chlorophenyl)ethyl]amino}ethylidene)-4-ethyl-5- methyl-3-thiophenecarboxylic acid methyl ester.
"Iprovalicarb" is a systemic fungicide used to control oomycete pathogens such as downy mildew, late blight, and other related diseases in various crops. It acts by inhibiting the synthesis of key components in the cell walls of the pathogens, thereby preventing their growth and spread. Iprovalicarb is effective when used as a preventative treatment and can be applied to a wide range of crops. Its chemical structure is represented by its IUPAC name: (RS)-2-methyl-l-{[l-(4- isopropylphenyl)ethyl]amino}carbonyl}cyclopropane-l-carboxylic acid.
In light of the invention, "mandipropamid" is a fungicide belonging to the carboxylic acid amide (CAA) class, used primarily to control oomycete pathogens such as downy mildew and late blight. It acts by inhibiting the biosynthesis of cellulose in the cell walls of the pathogens, leading to their death. Mandipropamid is known for its systemic and translaminar activity, providing both protective and curative effects. The chemical structure of mandipropamid is described by its IUPAC name: (RS)-2- {(2,6-dimethylphenyl)-methoxyacetylamino}-propionic acid methyl ester.
The method as described herein was found to be surprisingly effective in controlling a wide variety of oomycetes, even those that have developed resistance to carboxylic acid amide (CAA) fungicides, in particular dimethomorph, flumorph, pyrimorph, benthiavalicarb, iprovalicarb, and mandipropamid. This enhanced efficacy against CAA-resistant organisms not only improves control but also allows for the use of the method in integrated management strategies targeting a broad spectrum of oomycetes without the need to differentiate based on resistance profiles. Consequently, management strategies can be significantly simplified, making the described method broadly applicable and highly effective for most oomycete infestations.
According to a further or another embodiment, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 8: 1 and 1:4. By preference, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 6: 1 and 1:3, more by preference of between 4: 1 and 1 :2, even more by preference of between 3: 1 and 1 : 1. With increasing preference, the method was found to be more effective in controlling oomycete infestations such as described herein. Especially oomycete infestation encompassing CAA resistant strains, or even oomycete infestations encompassing both CAA resistant and CAA non-resistant strains, were found the be effectively controlled.
According to a further or another embodiment, said composition comprises: from 10 to 50 wt.% of valifenalate, and from 5 to 25 wt.% of cyazofamid, based on the total weight of the composition.
The method as described herein was found to be surprisingly effective in controlling a wide variety of oomycetes. Specifically, compositions comprising from 10 to 50 wt.% of valifenalate and from 5 to 25 wt.% of cyazofamid demonstrated enhanced efficacy against oomycetes, by preference CAA-resistant oomycetes. This combination not only improves control over CAA-resistant strains but also allows for a versatile management strategy targeting a broad spectrum of oomycetes without the need to differentiate based on resistance profiles. Consequently, management strategies can be significantly simplified, making the described method broadly applicable and highly effective for most oomycete infestations.
According to a further or another embodiment, said composition comprises from 5 to 80 wt.% of valifenalate, based on the total weight of the composition. By preference, said composition comprises from 10 to 60 wt.% of valifenalate, based on the total weight of the composition. More by preference, said composition comprises from 10 to 20 wt.% of valifenalate, based on the total weight of the composition.
According to a further or another embodiment, said composition comprises from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition. By preference, said composition comprises from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
Even more by preference, said composition comprises from 5 to 80 wt.% of valifenalate, and from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 10 to 60 wt.% of valifenalate, and from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. Even more by preference, said composition comprises from 10 to 20 wt.% of valifenalate, and from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
According to a further or another embodiment, said composition is formulated as a suspension concentrate (SC), an oil dispersion (OD), as a water dispersible granules (WG), as an emulsifiable concentrate (EC), as a concentrated oil-in-water emulsion (EW) as a wettable powder (WP), as a micro-emulsion (ME), as a capsule suspension (CS), as a suspoemulsion (SE), or as a mixed formulation of CS and SC (ZC).
A "suspension concentrate (SC)" is a type of liquid formulation where finely divided, insoluble active ingredients are suspended in water or another liquid carrier. This formulation is designed to be diluted with water before application, providing a convenient and effective means of delivering the active ingredient to the target pest. SC formulations are stable, easy to handle, and ensure uniform distribution of the active ingredient.
In light of the present invention, the wording "oil dispersion (OD)" must be interpreted as a stable suspension of active ingredients in a water immiscible fluid, which may optionally contain other dissolved active ingredients, intended for dilution with water before use.
The term "water dispersible granules (WG)" refers to a formulation consisting of granules to be applied after disintegration and dispersion in water.
An "emulsifiable concentrate (EC)" is to be read as a liquid, homogeneous formulation to be applied as an emulsion after dilution in water, more in particular, a liquid formulation consisting of a solvent, emulsifier, and the active ingredient.
A "concentrated oil-in-water emulsion (EW)" refers to a fluid, heterogeneous formulation consisting of a solution of pesticide in an organic liquid, dispersed as fine globules in a continuous water phase.
The wording "wettable powder (WP)" reads onto a powder formulation to be applied as a suspension after dispersion in water. It forms a suspension rather than a true solution, requiring agitation to stay mixed.
A "micro-emulsion (ME)" is a clear, stable, and fine emulsion with droplet sizes significantly smaller than those in a standard emulsion, or more in particular, a clear to opalescent, oil and water containing liquid, to be applied directly or after dilution in water, when it may form a diluted micro-emulsion or a conventional emulsion.
The term "capsule suspension (CS)" in light of the present invention is to be read as a formulation wherein the active ingredient is encapsulated in tiny, polymeric capsules suspended in a liquid, normally intended for dilution with water before use. This type provides controlled release of the active ingredient, reduced exposure risk, and can enhance stability and effectiveness.
A "suspoemulsion (SE)" is a fluid, heterogeneous formulation consisting of a stable dispersion of one or more active ingredients in the form of solid particles, and of fine globules immiscible with water in a continuous water phase. A "mixed formulation of CS and SC (ZC)" is a stable fluid suspension of capsules of one or more active ingredients combined with a suspension of fine particles of one or more active ingredients, normally intended for dilution with water before use.
According to some embodiments, said composition is formulated as a suspension concentrate (SC).
Suspension concentrate (SC) formulations offer numerous advantages for fungicide compositions in agricultural applications. These formulations may provide improved stability, ensuring that the active ingredient remains evenly dispersed and effective over extended storage periods. The liquid nature of SC formulations may allow for ease of handling, measuring, and mixing, reducing the risk of handling errors compared to dry formulations. This may also ensure uniform distribution of the fungicide when diluted with water, leading to consistent and thorough coverage of the target area. Additionally, SC formulations may eliminate the problem of dust generation, minimizing inhalation risks for applicators and reducing environmental contamination. The finely divided particles in SC formulations may furthermore enhance the bioavailability of the fungicide, promoting better absorption and efficacy against target pathogens. Moreover, SC formulations may also help mitigate phytotoxicity by reducing the concentration of potentially harmful solvents and adjuvants, ensuring safer application to crops. Compatibility with a wide range of other agricultural chemicals allows for tank-mixing and integrated pest management strategies. The minimized risk of spillage and wastage may make SC formulations more environmentally friendly. Overall, the user safety, environmental benefits, and enhanced performance make SC formulations were found to be an ideal choice for fungicide delivery in agriculture.
According to some other embodiments, said composition is formulated as an oil dispersion (OD). According to some other embodiments, said composition is formulated as water dispersible granules (WG). According to some other embodiments, said composition is formulated as an emulsifiable concentrate (EC). According to some other embodiments, said composition is formulated as a concentrated oil-in-water emulsion (EW). According to some other embodiments, said composition is formulated as a wettable powder (WP). According to some other embodiments, said composition is formulated as a micro-emulsion (ME). According to some other embodiments, said composition is formulated as a capsule suspension (CS). According to some other embodiments, said composition is formulated as a suspoemulsion (SE). According to some other embodiments, said composition is formulated as a mixed formulation of CS and SC (ZC).
According to a further or another embodiment, applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha.
In light of the present invention, "active ingredient (Al)" refers to the specific chemical or compound in a product that is responsible for its desired or primary effect. In the case of pesticides, the active ingredient is the substance that provides the pesticidal activity. It is distinct from other components of the formulation, such as carriers, solvents, or additives, which are used to enhance the product's stability, application, or safety. Application amounts may thus be expressed in "grams of active ingredient per hectare (g Al/ha)".
This broad range ensures flexibility in application, allowing for adjustments based on specific crop requirements and environmental conditions.
By preference, applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha. Most by preference, applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha. With increased preference, it has been shown that better balance is obtained between efficacy and crop safety, ensuring robust protection against oomycete pathogens.
According to a further or another embodiment, applying said composition comprises applying cyazofamid in an amount of between 50 and 120 g Al/ha.
This broad range provides versatility in combating various levels of oomycete infestation.
By preference, applying said composition comprises applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying cyazofamid in an amount of between 65 and 95 g Al/ha. Most by preference, applying said composition comprises applying cyazofamid in an amount of between 70 and 90 g Al/ha. With increased preference, it has been shown that more effective control is obtained with sustainable application rates, ensuring long-term crop protection and environmental safety.
According to a further or another embodiment, applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha.
This combination ensures broad-spectrum control and flexibility in managing various oomycete diseases.
By preference, applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha, and applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha, and applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha, and applying cyazofamid in an amount of between 65 and 95 g Al/ha. Most by preference, applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha, and applying cyazofamid in an amount of between 70 and 90 g Al/ha. With increased preference, it has been shown that higher levels of efficacy and resistance management are obtained, providing robust protection across a wide range of oomycete pathogens.
According to a further or another embodiment, said crop plant is selected from the group of potato crops, tomato crops, (grape)vine crops, cucurbit crops, lettuce crops, ornamental plants, or combinations thereof.
It was found that the method as described herein provides broad applicability across various important agricultural and horticultural crops, providing effective protection and control of oomycete pathogens that are known to affect these diverse plant species. The inclusion of potato and tomato crops addresses the critical need to manage late blight caused by Phytophthora infestans, which can devastate these staple crops. Grapevine crops benefit from protection against Plasmopara viticola, the causative agent of downy mildew, which significantly impacts grape production and quality. Cucurbit crops, including cucumbers, melons, and squashes, are safeguarded against Pseudoperonospora cubensis, responsible for downy mildew in these plants. Lettuce crops receive protection from Bremia lactucae, which causes downy mildew and can lead to severe crop losses. The embodiment also covers ornamental plants, which are often affected by Peronospora sparsa and other oomycete pathogens, ensuring the health and aesthetic value of these plants in both commercial and domestic settings. The ability to use this method across such a wide range of crops simplifies management strategies and enhances the overall efficacy of oomycete control measures.
According to some embodiments, said crop plant is selected from the group of potato crops. By preference, said potato crop is chosen from the group of Solanum tuberosum, Solanum andigenum, Solanum phureja, Solanum stenotomum, Solanum ajanhuiri, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of tomato crops. By preference, said tomato crop is chosen from the group of Solanum lycopersicum, Solanum pimpinellifolium, Solanum cheesmaniae, Solanum peruvianum, Solanum habrochaites, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of (grape)vine crops. By preference, said (grape)vine crop is chosen from the group of Vitis vinifera, Vitis labrusca, Vitis riparia, Vitis rotundifolia, Vitis amurensis, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of cucurbit crops. By preference, said cucurbit crop is chosen from the group ofCucumis sativus, Cucumis melo, Cucurbita pepo, Cucurbita maxima, Cucurbita moschata, Citrullus lanatus, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of lettuce crops. By preference, said lettuce crop is chosen from the group of Lactuca sativa, Lactuca sativa var. longifolia, Lactuca sativa var. crispa, Lactuca sativa var. capitata, Lactuca sativa var. angustana, or combinations thereof. According to some embodiments, said crop plant is selected from the group of ornamental plants. By preference, said ornamental plant is chosen from the group of Rosa spp., Chrysanthemum spp., Pelargonium spp., Petunia spp., Impatiens spp., Begonia spp., or combinations thereof.
It is noted that, salts and/or derivatives of valifenalate and/or cyazofamid are also falling within the above definitions of valifenalate and cyazofamid. Any salt may be possible as long as it is agriculturally acceptable. Examples thereof include alkali metal salts such as a sodium salt and a potassium salt, alkaline earth metal salts such as a magnesium salt and a calcium salt, ammonium salts such as a monomethylammonium salt, a dimethylammonium salt and a triethylammonium salt, inorganic acid salts such as a hydrochloride, a perchlorate, a sulfate and a nitrate salt, and organic acid salts such as an acetate and a methanesulfonate salt.
It is furthermore also noted that, although valifenalate has proven most efficiently in the method according to the first aspect of the present invention, alternative embodiments provide other carboxylic acid amide (CAA) fungicides that are formulated with cyazofamid. Relative amounts of such other carboxylic acid amide (CAA) fungicides may be included within the ranges disclosed above, or may be situated within other or broader ranges.
The fungicidal activity of fungicides comprising valifenalate or cyazofamid against oomycetes (including various species causing diseases such as late blight, downy mildew, and root rot) is already at a high level, but generally depends on factors such as the application rate, the specific formulation, the particular pathogen being targeted, and the climatic and soil conditions. Additional considerations include the duration of action and breakdown rate of the fungicide, its compatibility with different crop plants, the speed of action, the spectrum of activity, and its behavior towards subsequent crops (replanting issues) or general application flexibility (control of oomycetes at various growth stages). Changes in pathogen susceptibility, which may occur with prolonged use of the fungicides or in specific geographical regions (control of tolerant or resistant species of oomycetes), must also be taken into account. Increasing the application rates of fungicides to compensate for losses in action in resistant strains is only feasible to a certain degree, as this can reduce selectivity or fail to improve efficacy despite higher application rates. Thus, there is a frequent need for targeted synergistic activity against specific species of oomycetes, improved selectivity, generally lower amounts of active compounds for equally effective control, and reduced environmental impact to prevent issues such as leaching and carry-over effects. There is also a need for effective control of species that were previously uncontrolled (gaps) and for managing species that are tolerant or resistant to individual fungicides or multiple fungicides. Developing one-shot applications to avoid labor-intensive multiple applications and creating systems for controlling the rate of action, providing both rapid initial control and slow residual control, are also needed.
A possible solution to these problems may involve providing combined fungicide compositions, combining multiple fungicides and/or other components from the group of agrochemically active compounds of different types, along with formulation auxiliaries and additives commonly used in crop protection, which contribute desired additional properties. However, combining multiple active compounds often results in chemical, physical, or biological incompatibilities, such as decomposition of an active compound or antagonism in biological activity. Therefore, potentially suitable combinations of active compounds must be selected carefully and tested experimentally for their suitability, with the possibility of negative or positive outcomes not being safely discounted a priori.
Carboxylic acid amide (CAA) fungicides and fungicides belonging to the cyanoimidazole chemical group in some instances may exhibit an antagonistic effect when used in combination. The combination of valifenalate and cyazofamid has shown an unexpected reduction in antagonistic effects, and an increase in fungicidal activity. This enhanced activity was especially observed when combining valifenalate with cyazofamid according to the herein described weight ratios.
According to some embodiments, the composition comprises at least 1 wt.% of additional components, based on the total weight of the composition. More by preference, the composition comprises at least 5 wt.% of additional components, at least 10 wt.%, or at least 15 wt.% of additional components, based on the total weight of the composition. Even more by preference, the composition comprises at least 20 wt.%, at least 25 wt.%, at least 30 wt.%, at least 40 wt.%, or at least 50 wt.% of additional components, based on the total weight of the composition. According to some embodiments, the composition comprises at least 60 wt.%, at least 70 wt.%, at least 80 wt.%, or even at least 85 wt.% of additional components, based on the total weight of the composition.
According to some embodiments, said additional components are selected from the group comprising other pesticides such as herbicides, insecticides, fungicides, or other active pesticide ingredients, safeners, antioxidants, chemical stabilizers, adhesives, fertilizers, perfumes, colorants, liquid carriers, solid carriers, surfaceactive agents, crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, foaming agents, light-blocking agents, compatibility agents, antifoam agents, sequestering agents, neutralizing agents and buffers, wetting and dispersing agents, preservatives, thickening agents, corrosion inhibitors, freezing point depressants, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants, sticking agents and humectants, such as, for example, propylene glycol. According to preferred embodiments, the herbicide composition can also comprise various agrochemically active compounds, for example from the group of the acaricides, nematicides, bird repellants, and soil structure improvers.
The term "safener", as used throughout the description, is to be understood as a compound or a mixture of compounds which compensates for, or reduces, the phytotoxic properties of a pesticide towards crop plants without substantially reducing its pesticidal action.
Non-limiting examples of colorants include inorganic pigments such as iron oxide, titanium oxide and Prussian blue and/or organic dyes such as alizarin dyes, azo dyes and metal phthalocyanine, and trace elements such as iron, manganese, boron, copper, cobalt, molybdenum and zinc.
According to some embodiments, said additional components comprise herbicides selected from the group comprising acetochlor, acifluorfen, aclonifen, acrolein, AKH- 7088, alachlor, alloxydim, ametryn, amicarbazone, amidosulfuron, amitrole, ammonium sulfamate, anilofos, asulam, atrazine, azafenidin, azimsulfuron, BAS 625 H, beflubutamid, benazolin, benfluralin, benfuresate, bensulfuron-methyl, bensulide, bentazone, bifenox, bilanafos, bispyribac-sodium, borax, bromacil, bromobutide, bromoxynil, butachlor, butafenacil, butamifos, butralin, butroxydim, butylate, cafenstrole, carbetamide, carfentrazone-ethyl, chloramben, chlorbromuron, chlorflurenol-methyl, chloridazon, chlorimuron-ethyl, chloroacetic acid, chlorotoluron, chlorpropham, chlorsulfuron, chlorthal-dimethyl, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, clethodim, clodinafop-propargyl, clomazone, clomeprop, clopyralid, cloransulam-methyl, cumyluron, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cyhalofop-butyl, 2,4-D, daimuron, dalapon, dazomet, 2,4-DB, desmedipham, dicamba, dichlobenil, dichlorprop, dichlorprop-P, diclofop-methyl, diclosulam, difenzoquat metilsulfate, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethipin, dimethylarsinic acid, dinitramine, dinoterb, diphenamid, diquat dibromide, dithiopyr, diuron, DNOC, endothal, EPTC, esprocarb, ethalfluralin, ethametsulfuron-methyl, ethofumesate, ethoxysulfuron, etobenzanid, fenoxaprop-P-ethyl, fentrazamide, fenuron, ferrous sulfate, flamprop-M, flazasulfuron, florasulam, fluazifop-butyl, fluazifop-P-butyl, fluazolate, flucarbazone-sodium, fluchloralin, flufenacet, flumetsulam, flumiclorac-pentyl, flumioxazin, fluometuron, fluoroglycofen-ethyl, flupropanate, flupyrsulfuron-methyl-sodium, flurenol, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet-methyl, fomesafen, fosamine, glufosinate- ammonium, glyphosate, halauxyfen, halauxyfen-methyl, halosulfuron-methyl, haloxyfop, HC-252, hexazinone, imazamethabenz-methyl, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, iodosulfuron-methyl- sodium, ioxynil, isoproturon, isouron, isoxaben, lactofen, lenacil, linuron, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, mefenacet, mefluidide, metam, metamitron, metazachlor, methabenzthiazuron, methylarsonic acid, methyldymron, methyl isothiocyanate, metobenzuron, metobromuron, metolachlor, S-metolachlor, metosulam, metoxuron, metribuzin, metsulfuron-methyl, MK-616, MKH 6561, molinate, monolinuron, naproanilide, napropamide, naptalam, neburon, nicosulfuron, nonanoic acid, norflurazon, oleic acid (fatty acids), orbencarb, oryzalin, oxadiargyl, oxadiazon, oxasulfuron, oxaziclomefone, oxyfluorfen, paraquat dichloride, pebulate, pelargonic acid, pendimethalin, pentachlorophenol, pentanochlor, pentoxazone, petroleum oils, phenmedipham, picloram, picolinafen, piperophos, pretilachlor, primisulfuron-methyl, prodiamine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propyzamide, prosulfocarb, prosulfuron, pyraflufen-ethyl, pyrazosulfuron-ethyl, pyribenzoxim, pyributicarb, pyriminobac-methyl, pyrithiobac-sodium, quinclorac, quinmerac, quinoclamine, quizalofop, quizalofop-P, rimsulfuron, sethoxydim, siduron, simazine, simetryn, sodium chlorate, sulfentrazone, sulfometuron-methyl, sulfosulfuron, sulfuric acid, tar oils, 2,3,6-TBA, TCA-sodium, tebutam, tebuthiuron, tepraloxydim, terbacil, terbumeton, terbuthylazine, terbutryn, thenylchlor, thiazopyr, thifensulfuron-methyl, thiobencarb, tiocarbazil, tralkoxydim, tri-allate, triasulfuron, triaziflam, tribenuron-methyl, triclopyr, trietazine, trifluralin, triflusulfuron-methyl, and vernolate.
According to some embodiments, said additional components comprise insecticides selected from the group comprising 5-(2-chloropyrid-5-ylmethyl)-3-methyl-4- nitroiminoperhydro-l,3,5-oxadiazine, 5-(2-chlorothiazol-5-ylmethyl)-3-methyl-4- nitroiminoperhydro-l,3,5-oxadiazine, 3-methyl-4-nitroimino-5-(l-oxido-3- pyridinomethyl)perhydro-l,3,5-oxadiazine, 5-(2-chloro-l-oxido-5-pyridiniomethyl)- 3-methyl-4-nitroiminoperhydro-l,3,5-oxidiazine, 3-methyl-5-(2-methylpyrid-5- ylmethyl)-4-nitroiminoperhydro-l,3,5-oxadiazine, thiamethoxam (CAS RN 153719- 23-4), acetamiprid ((E)-N-[(6-chloro-3-pyridinyl)methyl]-N'-cyano-N- methyleneimidamide, CAS RN 135410-20-7), imidacloprid (l-[(6-chloro-3- pyridinyl)methyl]-N-nitro-2-imidazolidinimime, CAS RN 138261-41-3), nitenpyram (N-[(6-chloro-3-pyridinyl)methyl]-N-ethyl-N'-methyl-2-nitro-l,l-ethenediamine, CAS RN 120738-89-8), clothianidin (TI-435; N-[(2-chloro-5-thiazoyl)methyl]-N'- methyl-N"-nitro,[C(E)]-(9CI)-guanidine, CAS RN 210880-92-5), dinotefuran (N- methyl-N'-nitro-N"-[(tetrahydro-3-furanyl)methyl)]guanidine; CAS RN 165252-70- 0), acephate (CAS RN 30560-19-1), chlorpyrifos (CAS RN 2921-88-2), chlorpyrifos- methyl (CAS RN 5598-13-0), diazinon (CAS RN 333-41-5), fenamiphos (CAS RN 22224-92-6), malathion (CAS RN 121-75-5), aldicarb (CAS RN 116-06-3), carbaryl (CAS RN 63-25-2), carbofuran (CAS RN 1563-66-2), oxamyl (CAS RN 23135-22-0) and thiodicarb (CAS RN 59669-26-0).
According to some embodiments, said additional components comprise fungicides selected from the group comprising respiration inhibitors selected from the group comprising azoxystrobin, dimoxystrobin, enestroburin, fluoxastro-bin, kresoxim- methyl, meto-minostrobin, orysastrobin, picoxy-strobin, pyraclostrobin, pyrametostrobin, pyra oxyst robin, pyribencarb, trifloxystrobin, methyl(2-chloro-5 [1- (3-methylbenzyl-oxy-imino)-ethyl]benzyl)-carba-mate, 2 (2-(3-(2,6-di- chlorophenyl)-l-methyl-allylidene-aminooxy-methyl)-phenyl)-2-methoxyimino-N methyl-acetamide, famoxadone, fenamidone, benodanil, bixafen, boscalid, carboxin, fen-furam, fenhexamid, fluopyram, flutolanil, furametpyr, isopyrazam, isotianil, mepronil, oxycarboxin, penflufen, penthiopyrad, sedaxane, tecloftalam, thifluz- amide, tiadinil, 2-amino-4 methyl-thiazole-5-carbox-anilide, N-(3',4',5' tri-fluoro-bi- phenyl-2 yl)-3-difluoro-methyl-l-methyl-lH-pyrazole-4 carboxamide, N-(4'-tri- fluoro-methyl-thiobi-phenyl-2-yl)-3 difluoromethyl- 1-methyl-lH pyrazole-4-carbox- amide, N-(2-(l,3,3-trimethyl-butyl)-phenyl)-l,3-dimethyl-5 fluoro-lH-pyrazole-4 carbox-amide, amisulbrom, diflumetorim, binapacryl, dinobuton, dinocap, fluazinam, nitrthal-isopropyl, tecnazen, ferimzone, fentin salts, ametoctradin and silthiofam; sterol biosynthesis inhibitors (SBI fungicides) selected from the group comprising azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, diniconazole-M, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, paclobutrazole, penconazole, propiconazole, prothio-conazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, uniconazole, imazalil, pefurazoate, oxpoconazole, prochloraz, triflumizole, fenarimol, nuarimol, pyrifenox, triforine, aldimorph, dodemorph, dodemorph-acetate, fenpropimorph, tridemorph, fenpropidin, piperalin, spiroxamine, fenhexamid, benalaxyl, benalaxyl-M, kiralaxyl, metalaxyl, metalaxyl-M (mefenoxam), ofurace, oxadixyl, hymexazole, octhilinone, oxolinic acid, bupirimate, benomyl, carbendazim, fuberidazole, thiabendazole, thiophanate-methyl, 5-chloro-7(4-methyl-piperidin-l- yl)-6-(2,4,6-trifluorophenyl)-[l,2,4]tri-azolo-[l,5a]pyrimidine, diethofencarb, ethaboxam, pencycuron, fluopicolide, zoxamide, metrafenone, cyprodinil, mepanipyrim, nitrapyrin, pyrimethanil, blasticidin-S, kasugamycin, kasugamycin hydrochloride-hydrate, mildiomycin, streptomycin, oxytetracyclin, polyoxine, validamycin A, fluoroimid, iprodione, procymidone, vinclozolin, fenpiclonil, fludioxonil, quinoxyfen, edifenphos, iprobenfos, pyrazophos, isoprothiolane, dicloran, quintozene, tecnazene, tolclofos-methyl, biphenyl, chloroneb, etridiazole, dimethomorph, flumorph, mandiproamid, pyrimorph, benthiavalicarb, iprovalicarb, pyribencarb, N-(l-(l-(4-cyano-phenyl)-ethanesulfonyl)-but-2-yl) carbamic acid-(4- fluorophenyl) ester, propamocarb, propamo-carb-hydrochlorid, Bordeaux mixture, copper acetate, copper hydroxide, copper oxychloride, basic copper sulfate, sulfur, ferbam, mancozeb, maneb, metam, methasulphocarb, metiram, propineb, thiram, zineb, ziram, anilazine, chlorothalonil, captafol, captan, folpet, dichlofluanid, dichlorophen, flusulfamide, hexachlorobenzene, pentachlorphenole and its salts, phthalide, tolylfluanid, N-(4-chloro-2-nitro-phenyl)-N-ethyl-4-methyl- benzenesulfonamide, guanidine, dodine, dodine free base, guazatine, guazatine- acetate, iminoctadine, iminoctadine-triacetate, iminoctadine-tris(albesilate), dithianon, validamycin, polyoxin B, pyroquilon, tricyclazole, carpropamide, dicyclomet, fenoxanil, acibenzolar-S-methyl, probenazole, isotianil, tiadinil, prohexadione-calcium, fosetyl, fosetyl-aluminum, phosphorous acid and its salts, bronopol, chinomethionat, cyflufenamid, cymoxanil, dazomet, debacarb, diclomezine, difenzoquat, difenzoquat-methylsulfate, diphenylamin, flumetover, flusulfamide, flutianil, methasulfocarb, oxin-copper, proquinazid, tebufloquin, tecloftalam, triazoxide, 2-butoxy-6-iodo-3-propylchromen-4-one, N-(cyclo- propylmethoxyimino-(6-difluoro-methoxy-2,3-difluoro-phenyl)-methyl)-2-phenyl acetamide, N'-(4-(4-chloro-3-trifluoromethyl-phenoxy)-2,5-dimethyl-phenyl)-N- ethyl-N methyl formamidine, N' (4-(4-fluoro-3-trifluoromethyl-phenoxy)-2,5- dimethyl-phenyl)-N-ethyl-N-methyl formamidine, N'-(2-methyl-5-trifluoromethyl-4- (3-trimethyl-silanyl-prop-oxy)-phenyl)-N-ethyl-N-methyl formamidine, N'-(5- difluoromethyl-2 methyl-4-(3-tri-methylsilanyl-propoxy)-phenyl)-N-ethyl-N-methyl formamidine, 2-{l-[2-(5-methyl-3-trifluoromethyl-pyrazole-l-yl)-acetyl]-piperidin- 4-yl}-thiazole-4-carboxylic acid methyl-( 1,2,3, 4-tetrahydro-na phthalen-l-yl)- amide, 2-{l-[2-(5-meth-yl-3-trifluoromethyl-pyrazole-l-yl)-acetyl]-piperidin-4- yl}-thiazole-4-carboxylic acid methyl-(R)-l,2,3,4-tetrahydro-naphthalen-l-yl- amide, methoxy-acetic acid 6-tert-butyl-8-fluoro-2,3-dimethyl-quinolin-4-yl ester, N-Methyl-2-{l-[(5-methyl-3-trifluoro-methyl-lH-pyr-azol-l-yl)-acetyl]-piperi-din- 4-yl}-N-[( 1R)- 1,2, 3, 4-tetrahydro-na phthalen-l-yl]-4-thi-azolecarboxamide, 3-[5- (4-chloro-phenyl)-2,3-dimethyl-isoxazolidin-3 yl]-pyridine, 3-[5-(4-methyl-phenyl)-
2.3-dimethyl-isoxazolidin-3-yl]-pyridine, 5-amino-2-iso-propyl-3-oxo-4-ortho-tolyl-
2.3-dihydro-pyrazole-l carbo-thioic acid S-allyl ester, N-(6-methoxy-pyridin-3- yl)cyclopropanecarboxylic acid amide, 5-chloro-l (4,6-dimethoxy-pyrimidin-2-yl)-2- methyl-lH-benzoimidazole, 2-(4-chloro-phenyl)-N-[4-(3,4-dimeth-oxy-phenyl)- isoxazol-5-yl]-2-prop-2-ynyloxy-acetamide, abscisic acid, amidochlor, ancymidol, 6- benzylaminopurine, brassinolide, butralin, chlormequat (chlormequat chloride), choline chloride, cyclanilide, daminozide, dike-gulac, dimethipin, 2,6- dimethylpuridine, ethephon, flumetralin, flurprimidol, fluthi-acet, forchlorfenuron, gibberellic acid, inabenfide, indole-3-acetic acid, maleic hydrazide, mefluidide, mepiquat (mepiquat chloride), naphthaleneacetic acid, N 6 benzyladenine, paclobutrazol, prohexadione (prohexadione-calcium), prohydrojasmon, thidiazuron, triapenthenol, tributyl phosphorotrithioate, 2,3,5 tri iodobenzoic acid, trinexapac- ethyl and uniconazole, and antifungal biocontrol agents.
According to some embodiments, said additional components comprise agricultural adjuvants and/or carriers. More in particular, according to some embodiments, said additional components comprise liquid carriers, solid carriers, surface-active agents, or combinations thereof.
According to some embodiments, said liquid carriers are water and/or solvents selected from the group comprising toluene, xylene, petroleum naphtha, p-diethyl benzene, isopropyl benzene, m-xylene, o-xylene, p-xylene; cyclohexane, hexadecane, isooctane, n-hexane; paraffin oil, mineral oil, crop oil; chlorobenzene, 1,2-dichloropropane, 1.1. -trichloroethane, methylene chloride, trichloroethylene, perchloroethylene; alpha-pinene, d-limonene; lactic acid and ester derivatives, such as methyl lactate, ethyl lactate, butyl lactate, 2-ethylhexyl lactate; octadecanoic acid, oleic acid, propionic acid, xylene sulphonic acid and their ester forms; cyclohexanol, diacetone alcohol, diethylene glycol, dipropylene glycol, 2-ethyl hexanol, ethylene glycol, phenol, polyethylene glycol (PEG400), propylene glycol, triethylene glycol, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetra hydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, benzyl alcohol; acetone, methyl ethyl ketone, cyclohexanone, acetophenone, 2-butanone, 2-heptanone, gamma-butyrolactone, glycerol, isophorone, mesityl oxide, methyl isoamyl ketone, methyl isobutyl ketone; diethylene glycol butyl ether, diethylene glycol ethyl ether, 1,4-dioxane, dipropylene glycol methyl ether, propylene glycol ethers (diproxitol), ethylene glycol butyl ether, ethylene glycol methyl ether, methoxy propanol, propylene glycol monomethyl ether; alkyl acetates such as ethyl acetate, propyl acetate, n-butyl acetate, amyl acetate, isoamyl acetate, isobornyl acetate, octyl amine acetate, glycerol monoacetate, glycerol diacetate, glycerol triacetate, 2-ethyl hexyl stearate, methyl oleate, n-butyl oleate, isopropyl myristate, methyl laurate, methyl octanoate, diethylene glycol abietate, dipropylene glycol dibenzoate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate, triethyl phosphate, dibasic esters (dimethyl glutarate + dimethyl succinate + dimethyl adipate), butyl benzoate; ethylene carbonate, propylene carbonate and butylene carbonate; diethanolamine, laurylamine, n-octylamine, oleylamine; N,N-dimethyl alkylamides such as N,N- dimethyl formamide, N,N-dimethylacetamide, N,N-dimethyl octan/decanamide, N,N-dimethyl decanamide, N,N-dimethyl dodecanamide, dimethyl lactamide; methyl 5-(dimethylamino)-4-methyl-5-oxopentanote; alkyl pyrrolidinones, such as N- methyl-2-pyrrolidinone, N-ethyl-2-pyrrolidinone; dimethyl sulfoxide; acetonitrile; acetic anhydride; and the like, soybean oil, rapeseed oil, sunflower seed oil, corn oil, cotton seed oil, linseed oil, safflower oil, olive oil, peanut oil, castor oil, palm oil, coconut oil, sesame oil, tung oil and the like; esters of the above vegetable oils, and the like.
According to some embodiments, said solid carriers include talc, titanium dioxide, pyrophyllite clay, silica, kaolin clay, attapulgite clay, kieselguhr, chalk, diatomaceous earth, lime, montmorillonite clay, lime, calcium carbonate, bentonite clay, fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood floor, walnut shell flour, lignin, cellulose and the like.
A broad range of surface-active agents are advantageously employed in the above- mentioned compositions, especially those designed to be diluted with carrier before application. "Surface-active agents", also known as surfactants, are compounds that lower the surface tension (or interfacial tension) between two liquids or between a liquid and a solid.
According to some embodiments, said surface-active agents are anionic, cationic, non-ionic or polymeric in character and may act as detergents, wetting agents, emulsifiers, foaming agents, and dispersants. Many organic compounds exhibit some surface-active properties; however specifically for the purposes of the invention nonionic surface-active agents can be used. Prominent among these are the fatty alcohols, such as cetyl alcohol, stearyl alcohol, and cetostearyl alcohol (consisting predominantly of cetyl and stearyl alcohols), and oleyl alcohol; but also polyethylene glycol alkyl ethers such as octaethylene glycol monododecyl ether and pentaethylene glycol monododecyl ether; polypropylene glycol alkyl ethers; polyethylene glycol - polypropylene glycol alkyl ethers; glucoside alkyl ethers such as decyl glucoside, lauryl glucoside or octyl glucoside; polyethylene glycol octylphenyl ethers; polyethylene glycol nonylphenyl ethers; polyethylene glycol tributylphenyl ethers; polyethylene glycol tristyryl phenyl ethers; polyethylene glycol - polypropylene glycol tristyrylphenyl ethers; glycerol alkyl esters such as glyceryl laurate; polyoxyethylene glycol sorbitan alkyl esters, such as polysorbates; sorbitan alkyl esters, such as spans; cocamide MEA or DEA; dodecyldimethylamine oxide; block copolymers of polyethylene glycol and polypropylene glycol, such as poloxamers; polyethoxylated tallow amine (POEA); vegetable oil ethoxylates, such as castor oil ethoxylates, rapeseed oil ethoxylates, soybean oil ethoxylates; and the like, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di-(2-ethyl hexyl) sulfosuccinate; salts of mono and dialkyl phosphate esters; quaternary amines, such as lauryl trimethylammonium chloride and the like. According to some embodiments, the compositions may further comprise liquid and solid fertilizers, such as particulate fertilizers like ammonium nitrate, urea and the like.
In a preferred embodiment, said additional components comprise one or more compounds that function to improve crop plant compatibility, selected from the group comprising 4-dichloroacetyl-l-oxa-4-aza-spiro[4.5]-decane (AD-67, MON- 4660), l-dichloro-acetyl-hexahydro-3,3,8a-trimethylpyrrolo[l,2-a]-pyrimidin- 6(2H)-one (dicyclonon, BAS-145138), 4-dichloroacetyl-3,4-dihydro-3-methyl-2H- 1,4-benzoxazine (benoxacor), 1-methyl-hexyl 5-chloro-quinolin-8-oxy-acetate (cloquintocet-mexyl— cf. also related compounds in EP-A-86750, EP-A-94349, EP-A- 191736, EP-A-492366), 3-(2-chloro-benzyl)-l-(l-methyl-l-phenyl-ethyl)-urea
(cumyluron), o-(cyano methoximino)-phenylacetonitrile (cyometrinil), 2,4-dichloro- phenoxyacetic acid (2,4-D), 4-(2,4-dichloro-phenoxy)-butyric acid (2,4-DB), 1-(1- methyl-l-phenyl-ethyl)-3-(4-methyl-phenyl)-urea (daimuron, dymron), 3,6- dichloro-2-methoxy-benzoic acid (dicamba), S-l-methyl-l-phenyl-ethyl piperidine-
1-th iocarboxylate (dimepiperate), 2,2-dichloro-N-(2-oxo-2-(2-propenylamino)- ethyl)-N-(2-propenyl)-acetamide (DKA-24), 2,2-dichloro-N,N-di-2-propenyl- acetamide (dichlormid), 4,6-dichloro-2-phenyl-pyrimidine (fenclorim), ethyl l-(2,4- dichloro-phenyl)-5-trichloromethyl-lH-l,2,4-triazole-3-carboxylate (fenchlorazole- ethyl— cf. also related compounds in EP-A-174562 and EP-A-346620), phenylmethyl
2-chloro-4-trifluoromethyl-thiazole-5-carboxylate (flurazole), 4-chloro-N-(l,3- dioxolan-2-yl-methoxy)-o-trifluoro acetophenone oxime (fluxofenim), 3- dichloroacetyl-5-(2-furanyl)-2,2-dimethyl-oxazolidine (furilazole, MON- 13900), ethyl 4,5-dihydro-5,5-diphenyl-3-isoxazolecarboxylate (isoxadifen-ethyl— cf. also related compounds in WO-A-95/07897), l-(ethoxycarbonyl)-ethyl 3,6-dichloro-2- methoxybenzoate (lactidichlor), (4-chloro-o-tolyloxy)-acetic acid (MCPA), 2-(4- chloro-o-tolyloxy)-propionic acid (mecoprop), diethyl l-(2,4-dichloro-phenyl)-4,5- dihydro-5-methyl-lH-pyrazole-3,5-dicarboxylate (mefenpyr-diethyl— cf. also related compounds in WO-A-91/07874), 2-dichloromethyl-2-methyl-l,3-dioxolane (MG- 191), 2-propenyl-l-oxa-4-azaspiro[4.5]decane 4-carbodithioate (MG-838), 1,8- naphthalic anhydride, o-(l,3-dioxolan-2-yl-methoximino)-phenylacetonitrile (oxabetrinil), 2,2-dichloro-N-(l,3-dioxolan-2-yl-methyl)-N-(2-propenyl)-acetamide (PPG-1292), 3-dichloroacetyl-2,2-dimethyl-oxazolidine (R-28725), 3-dichloroacetyl- 2,2,5-trimethyl-oxazolidine (R-29148), 4-(4-chloro-o-tolyl)-butyric acid, 4-(4- chloro-phenoxy)-butyric acid, diphenylmethoxyacetic acid, methyl diphenylmethoxyacetate, ethyl diphenyl-methoxyacetate, methyl l-(2-chloro- phenyl)-5-phenyl-lH-pyrazole-3-carboxylate, ethyl l-(2,4-dichloro-phenyl)-5- methyl-lH-pyrazole-3-carboxylate, ethyl l-(2,4-dichloro-phenyl)-5-isopropyl-lH- pyrazole-3-carboxylate, ethyl l-(2,4-dichloro-phenyl)-5-(l,l-dimethyl-ethyl)-lH- pyrazole-3-carboxylate, ethyl l-(2,4-dichloro-phenyl)-5-phenyl-lH-pyrazole-3- carboxylate (cf also related compounds in EP-A-269806 and EP-A-333131), ethyl 5- (2,4-dichloro-benzyl)-2-isoxazoline-3-carboxylate, ethyl 5-phenyl-2-isoxazoline-3- carboxylate, ethyl 5-(4-fluoro-phenyl)-5-phenyl-2-isoxazoline-3-carboxylate (cf. also related compounds in WO-A-91/08202), 1,3-dimethyl-but-l-yl 5-chloro- quinolin-8-oxy-acetate, 4-allyloxy-butyl 5-chloro-quinolin-8-oxy-acetate, 1-allyloxy- prop-2-yl 5-chloro-quinolin-8-oxy-acetate, methyl 5-chloro-quinoxalin-8-oxy- acetate, ethyl 5-chloro-quinolin-8-oxy-acetate, allyl 5-chloro-quinoxalin-8-oxy- acetate, 2-oxo-prop-l-yl 5-chloro-quinolin-8-oxy-acetate, diethyl 5-chloro-quinolin- 8-oxy-malonate, diallyl 5-chloro-quinoxalin-8-oxy-malonate, diethyl 5-chloro- quinolin-8-oxy-malonate (cf. also related compounds in EP-A-582198), 4-carboxy- chroman-4-yl-acetic acid (AC-304415, cf. EP-A-613618), 4-chloro-phenoxy-acetic acid, 3,3'-dimethyl-4-methoxy-benzophenone, l-bromo-4-chloromethylsulphonyl- benzene, l-[4-(N-2-methoxybenzoylsulphamoyl)-phenyl]-3-methyl-urea (alias N- (2-methoxy-benzoyl)-4-[(methylamino-carbonyl)-amino]-benzenesulphonamide), l-[4-(N-2-methoxybenzoylsulphamoyl)-phenyl]-3,3-dimethyl-urea, l-[4-(N-4,5- dimethylbenzoylsulphamoyl)-phenyl]-3-methyl-urea, l-[4-(N- naphthylsulphamoyl)-phenyl]-3,3-dimethyl-urea, and N-(2-methoxy-5-methyl- benzoyl)-4-(cyclopropylaminocarbonyl)-benzenesulphonamide.
A second aspect of the present invention concerns a fungicide composition comprising valifenalate and cyazofamid, wherein said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1 :5.
The several embodiments and their accompanying advantages of the first aspect of the invention, if compatible, are equally embodiments of the composition according to the second aspect of the invention. In particular, preferred ranges, concentrations, and/or additional components of the composition used in the method according to the first aspect, may be equally applicable to the composition of the second aspect.
By preference, the fungicide composition is for use in a method according to first aspect of the invention. According to some embodiments, the composition of the invention may be applied as a tank mix comprising two or more tank mix parts. A first tank mix part herein comprises at least said valifenalate and said cyazofamid, and a second tank mix part may comprise one or more additional components as described in any of the aforementioned embodiments.
According to some embodiments, the composition of the invention may be applied as part of an application program, wherein a first application comprises applying at least said valifenalate and said cyazofamid. In a subsequent second, third or fourth application, one or more additional components as described in any of the aforementioned embodiments may be applied.
A third aspect of the present invention concerns a method of improving plant resistance against pests and/or inducing plant defense pathways, said method comprising: providing a composition comprising valifenalate and cyazofamid, and applying said composition to a crop plant, a pest population associated with a crop plant, a habitat of a crop plant, or a combination thereof, characterized in that, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1 :5, and wherein said pest population comprises at least one organism chosen from the group of oomycetes.
The wording "plant resistance against pests" refers to the inherent or induced ability of a plant to prevent, mitigate, or withstand damage caused by biotic stressors, such as insects, nematodes, fungi, bacteria, viruses, or other plant pests. This resistance may be achieved through various mechanisms, including but not limited to structural barriers, biochemical pathways, or genetic modifications. Structural barriers, such as waxy cuticles or trichomes, may physically deter pest infestation, while biochemical pathways may involve the production of secondary metabolites, proteins, or enzymes that are toxic or repellent to pests.
The wording "inducing plant defense pathways" need be interpreted as activating or augmenting the plant's natural or engineered defense mechanisms in response to external stimuli, including pest attacks or environmental signals. Such pathways may for example include the jasmonic acid (JA), salicylic acid (SA), or ethylene signaling pathways, which regulate the expression of defense-related genes. Induction of these pathways may enhance the production of phytoalexins, pathogenesis-related (PR) proteins, or other antimicrobial compounds. Such induction may for example occur via external application of elicitors, such as chemical inducers, biological agents (e.g., beneficial microbes), or RNA-based technologies, or through environmental stimuli like mechanical damage or UV light exposure. These pathways may furthermore be harnessed or enhanced by genetic engineering, breeding strategies, or precision agriculture techniques to optimize the plant's resistance to pests or pathogens.
It was now unexpectedly found that the combination of valifenalate and cyazofamid in the ratios as described herein allows that a target crop plant effectively obtains a better resistance against pest infestations and/or that plant defense pathways are induced in the target crop plant, which actively helps in fighting off pest infestations. The herein described resistance and/or pathways provide an alternative or additional mode of action against pests, allowing the crop plant to better thrive in its habitat by preventing, mitigating or withstanding any possible damage or negative effects caused by pests.
By preference, improving plant resistance against pests and/or inducing plant defense pathways comprises inducing overexpression of one or more plant defense genes.
The terminology "overexpression of genes" refers to the increased production or accumulation of a specific protein, polypeptide, or RNA molecule in a cell or organism, relative to its natural or basal expression levels.
The wording "plant defense genes" need be interpreted as genes that encode proteins, peptides, metabolites, signaling molecules, or RNA molecules involved in recognizing, responding to, or mitigating biotic or abiotic stress. These genes may function directly by producing antimicrobial peptides, enzymes, structural proteins, or metabolites such as alkaloids or polyphenols; or indirectly by regulating signaling pathways that activate defense responses. Examples include genes encoding pathogenesis-related (PR) proteins, receptor-like kinases, and enzymes involved in the biosynthesis of secondary metabolites.
According to a further or another embodiment, improving plant resistance against pests and/or inducing plant defense pathways comprises inducing one or more plant defense pathways chosen from the group consisting of systemic acquired resistance pathways, in particular PR protein pathways, phenylpropanoid pathways, oxidative stress pathways, salicylic acid pathways, jasmonic acid pathways, or combinations thereof.
In light of the invention, "systemic acquired resistance (SAR) pathways" refer to plant-wide defense mechanisms activated following localized exposure to a pathogen or stressor. SAR pathways involve the translocation of signaling molecules, such as salicylic acid or its derivatives, to uninfected parts of the plant, leading to the activation of defense-related genes. This response confers long-lasting and broadspectrum resistance against subsequent pathogen attacks.
Pathways involving "pathogenesis-related (PR) proteins" encompass the biochemical and molecular processes by which plants produce PR proteins in response to biotic or abiotic stress. These proteins, such as chitinases, glucanases, and defensins, function as antimicrobial agents or regulators of the plant immune system. PR protein pathways are often activated by signaling molecules, including salicylic acid, and contribute to both local and systemic resistance mechanisms.
"Phenylpropanoid pathways" refer to a series of enzymatic reactions in plants that produce phenolic compounds derived from phenylalanine. These pathways play a critical role in plant defense by synthesizing secondary metabolites, such as lignins, flavonoids, and phytoalexins, which reinforce structural barriers, provide antioxidant properties, or exhibit antimicrobial activity. Key enzymes in this pathway include phenylalanine ammonia-lyase (PAL) and chaicone synthase (CHS).
"Oxidative stress pathways" are cellular defense mechanisms activated in response to the accumulation of reactive oxygen species (ROS) caused by biotic or abiotic stress. These pathways regulate the production of antioxidant molecules and enzymes, such as catalases, peroxidases, and superoxide dismutases, to detoxify ROS and protect cellular components from oxidative damage. Oxidative stress pathways also serve as signaling mechanisms that activate broader defense responses.
"Salicylic acid pathways" are biochemical and molecular signaling cascades in plants that mediate defense responses to biotrophic pathogens and abiotic stress. These pathways regulate the activation of SAR, PR protein expression, and the production of antimicrobial metabolites. Salicylic acid acts as both a signaling molecule and a regulator of downstream defense genes involved in local and systemic resistance.
"Jasmonic acid pathways" are signaling pathways that mediate plant defense responses against herbivorous insects, necrotrophic pathogens, and mechanical damage. Jasmonic acid and its derivatives act as signaling molecules that activate genes involved in the synthesis of defensive compounds, such as proteinase inhibitors and secondary metabolites. These pathways interact with other hormonal signaling networks, including salicylic acid and ethylene, to fine-tune defense responses.
It was found that the combination of valifenalate and cyazofamid in the ratios as described herein allows that a target crop plant shows induction of the defense pathways described herein, which actively helps in fighting off pest infestations.
According to a further or another embodiment, said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR5, PR8, PR14, PR15, PAL, CHS, DFR, ANS, PPO, HMGR, FPPS, Far, CSL, Apox, GST, POX, CalS, Peet, CAD, EDS1, WRKY, Lox2, JAR, ACCO, EIN3, or combinations thereof.
According to a further or another embodiment, said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR5, PR8, PR14, PR15, or combinations thereof. This group of plant defense genes preferably relates to the pathogenesis- related (PR) proteins pathway.
According to a further or another embodiment, said plant defense genes are chosen from the group consisting of PAL, CHS, DFR, ANS, PPO, or combinations thereof. This group of plant defense genes preferably relates to the phenylpropanoid pathways.
According to a further or another embodiment, said plant defense genes are chosen from the group consisting of HMGR, FPPS, Far, or combinations thereof. This group of plant defense genes preferably relates to the isoprenoid pathway.
According to a further or another embodiment, said plant defense genes are chosen from the group consisting of Apox, GST, POX, or combinations thereof. This group of plant defense genes preferably relates to the antioxidant system pathway. According to a further or another embodiment, said plant defense genes are chosen from the group consisting of EDS1, WRKY, or combinations thereof. This group of plant defense genes preferably relates to the salicylic acid signaling pathway.
According to a further or another embodiment, said plant defense genes are chosen from the group consisting of Lox2, JAR, or combinations thereof. This group of plant defense genes preferably relates to the jasmonic acid signaling pathway.
According to a further or another embodiment, characterized in that, said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR8, GST, POX, EDS1, WRKY, Lox2, or combinations thereof.
According to some embodiments, said method comprises observing a defense response lasting for at least 72 hours after applying said composition.
According to a further or another embodiment, said method comprises inducing said plant defense pathways in the absence of pathogens or additional stimuli.
According to some embodiments, said pest population comprises at least one organism chosen from the group of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
According to a further or another embodiment, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 8: 1 and 1 :4. By preference, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 6: 1 and 1:3, more by preference of between 4: 1 and 1 :2, even more by preference of between 3: 1 and 1 : 1. With increasing preference, the method was found to be more effective in improving plant resistance against pests and/or inducing plant defense pathways.
According to a further or another embodiment, said composition comprises from 10 to 50 wt.% of valifenalate, and from 5 to 25 wt.% of cyazofamid, based on the total weight of the composition.
The method as described herein was found to be surprisingly effective in improving plant resistance against pests and/or inducing plant defense pathways. Specifically, compositions comprising from 10 to 50 wt.% of valifenalate and from 5 to 25 wt.% of cyazofamid demonstrated enhanced elicitor effects.
According to a further or another embodiment, said composition comprises from 5 to 80 wt.% of valifenalate, based on the total weight of the composition. By preference, said composition comprises from 10 to 60 wt.% of valifenalate, based on the total weight of the composition. More by preference, said composition comprises from 10 to 20 wt.% of valifenalate, based on the total weight of the composition.
According to a further or another embodiment, said composition comprises from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition. By preference, said composition comprises from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
Even more by preference, said composition comprises from 5 to 80 wt.% of valifenalate, and from 2 to 50 wt.% of cyazofamid, based on the total weight of the composition. More by preference, said composition comprises from 10 to 60 wt.% of valifenalate, and from 6 to 40 wt.% of cyazofamid, based on the total weight of the composition. Even more by preference, said composition comprises from 10 to 20 wt.% of valifenalate, and from 5 to 15 wt.% of cyazofamid, based on the total weight of the composition.
According to a further or another embodiment, said composition is formulated as a suspension concentrate (SC), an oil dispersion (OD), as a water dispersible granules (WG), as an emulsifiable concentrate (EC), as a concentrated oil-in-water emulsion (EW) as a wettable powder (WP), as a micro-emulsion (ME), as a capsule suspension (CS), as a suspoemulsion (SE), or as a mixed formulation of CS and SC (ZC).
By preference, said composition is formulated as a suspension concentrate (SC).
According to some embodiments, applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha. By preference, applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha. Most by preference, applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha. With increased preference, it has been shown that better balance is obtained between efficacy and crop safety.
According to a further or another embodiment, applying said composition comprises applying cyazofamid in an amount of between 50 and 120 g Al/ha.
By preference, applying said composition comprises applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying cyazofamid in an amount of between 65 and 95 g Al/ha. Most by preference, applying said composition comprises applying cyazofamid in an amount of between 70 and 90 g Al/ha. With increased preference, it has been shown that more effective control is obtained with sustainable application rates, ensuring long-term crop protection and environmental safety.
According to a further or another embodiment, applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha.
By preference, applying said composition comprises applying valifenalate in an amount of between 110 and 180 g Al/ha, and applying cyazofamid in an amount of between 55 and 110 g Al/ha. More by preference, applying said composition comprises applying valifenalate in an amount of between 120 and 170 g Al/ha, and applying cyazofamid in an amount of between 60 and 100 g Al/ha. Even more by preference, applying said composition comprises applying valifenalate in an amount of between 130 and 165 g Al/ha, and applying cyazofamid in an amount of between 65 and 95 g Al/ha. Most by preference, applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha, and applying cyazofamid in an amount of between 70 and 90 g Al/ha. With increased preference, it has been shown that higher levels of efficacy and resistance management are obtained.
According to a further or another embodiment, said crop plant is selected from the group of potato crops, tomato crops, (grape)vine crops, cucurbit crops, lettuce crops, ornamental plants, or combinations thereof.
It was found that the method as described herein provides broad applicability across various important agricultural and horticultural crops, providing effective protection and control of oomycete pathogens that are known to affect these diverse plant species. The inclusion of potato and tomato crops addresses the critical need to manage late blight caused by Phytophthora infestans, which can devastate these staple crops. Grapevine crops benefit from protection against Plasmopara viticola, the causative agent of downy mildew, which significantly impacts grape production and quality. Cucurbit crops, including cucumbers, melons, and squashes, are safeguarded against Pseudoperonospora cubensis, responsible for downy mildew in these plants. Lettuce crops receive protection from Bremia lactucae, which causes downy mildew and can lead to severe crop losses. The embodiment also covers ornamental plants, which are often affected by Peronospora sparsa and other oomycete pathogens, ensuring the health and aesthetic value of these plants in both commercial and domestic settings. The ability to use this method across such a wide range of crops simplifies management strategies and enhances the overall efficacy of pest control.
According to some embodiments, said crop plant is selected from the group of potato crops. By preference, said potato crop is chosen from the group of Solanum tuberosum, Solanum andigenum, Solanum phureja, Solanum stenotomum, Solanum ajanhuiri, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of tomato crops. By preference, said tomato crop is chosen from the group of Solanum lycopersicum, Solanum pimpinellifolium, Solanum cheesmaniae, Solanum peruvianum, Solanum habrochaites, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of (grape)vine crops. By preference, said (grape)vine crop is chosen from the group of Vitis vinifera, Vitis labrusca, Vitis riparia, Vitis rotundifolia, Vitis amurensis, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of cucurbit crops. By preference, said cucurbit crop is chosen from the group ofCucumis sativus, Cucumis melo, Cucurbita pepo, Cucurbita maxima, Cucurbita moschata, Citrullus lanatus, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of lettuce crops. By preference, said lettuce crop is chosen from the group of Lactuca sativa, Lactuca sativa var. longifolia, Lactuca sativa var. crispa, Lactuca sativa var. capitata, Lactuca sativa var. angustana, or combinations thereof.
According to some embodiments, said crop plant is selected from the group of ornamental plants. By preference, said ornamental plant is chosen from the group of Rosa spp., Chrysanthemum spp., Pelargonium spp., Petunia spp., Impatiens spp., Begonia spp., or combinations thereof.
The several embodiments and their accompanying advantages of the first and second aspects of the invention, if compatible, are equally embodiments of the method according to the third aspect of the invention. In particular, preferred ranges, concentrations, and/or additional components of the composition according to the second aspect, or as used in the method according to the first aspect, may be equally applicable to the method of the third aspect.
According to some preferred embodiments, the composition according to the second aspect is used in a method according to the third aspect of the invention.
EXAMPLES
Example 1. Controlling Phytophthora infestans in potato according to some embodiments of the invention.
Pest organisms
Treatments were conducted on a CAA resistant strain (genotype EU43_A1) of Phytophthora infestans, as shown in Table 1. Table 1. Overview of pest organism strains.
Potato crop plants were infected with CAA resistant genotype EU43_A1.
Crop plants
Pre-germinated potato tubers ("Bintje" cultivar) were planted in 500 mL pots and stored in greenhouse conditions to grow. A first treatment was performed as soon as the crop plants were 20 to 25 cm tall.
Treatments
The crop plants were treated with a boom sprayer in the greenhouse, with a water volume of 200 L/ha. The treatments, in particular their composition and application dosage, are summarized in Table 2.
Table 2. Overview of treatments.
Conduction of trials
Ten potato plants were used per treatment, per genotype, each plant being a replicate. Products were applied at dose rates as mentioned in Table 2. One day after the treatment, the crop plants were placed in an infection hall to be infected (inoculated) with EU43_A1. A greenhouse fogging system was set to highest humidity level the night following the inoculation to ensure a good development of Phytophthora infestans. The day after the inoculation, the crop plants were moved to the climate chamber. Conditions were as follows: a temperature of between 18 and 20 °C, a humidity of between 75 and 90 %, and a light/dark schedule of 16h/8h light/dark. Symptoms were followed up every day from 3 days after the infection.
The following days after the inoculation, plants were checked daily to monitor the emergence of the disease. Assessments were made once the first symptoms were visible, both a COUDIS (Number of spots/leaf) and a PESSEV (% leaf surface destroyed by pathogen) assessment were made at regular intervals when the first symptoms were emerging.
Once the infection became too severe to count spots, each pot was scored as a whole for % disease severity, for example by rating the pot in relation to the appropriate % disease category described below in terms of average numbers of spots per plant, number of leaflets attacked, the form of the plants and the general appearance of the pot.
Percent disease severity is defined as follows:
0 = no infection;
1 = up to 5 spots per plant or up to 1 leaflet in 10 attacked;
5 = around 25 spots per plant or up to 1 leaflet in 10 attacked;
10 = up to 4 leaflets in 10 affected, plants still remaining normal form;
25 = nearly every leaflet with lesions but plants still retaining normal form, plot may look green though every plant affected; and
50 = every plant affected and about half of leaf area destroyed by blight, plot looks green, flecked with brown.
Consequently, efficacy was calculated using the following formula:
Efficacy (%) = (severityuTc - severitytreatment) I (severityuTc) x 100 and synergistic effect was calculated according to the Colby formula as described, wherein results lower or higher than 1 show antagonism or synergism respectively.
Results
The test results of Example 1 are shown in Table 3. Table 3. Test results regarding the control of Phytophthora infestans (genotype EU43_A1, CAA resistant) in potato according to some embodiments of the invention.
(*) Days After Inoculation (DAI)
From these results, it is clearly shown that for the CAA resistant strain of Phytophthora infestans, the mere combination of valifenalate and cyazofamid in e.g. a tank mix, leads to a light to moderate antagonistic effect (Colby 4). Upon treatment with a composition according to the invention however, the effect is at least additive, or even synergistic (Colby 5).
On the other hand, in CAA sensitive strains of Phytopthora infestans, efficacy of valifenalate and cyazofamid was generally found to be unaffected or even improved by using a composition according to the invention, compared to using a tank mix of the separate formulations.
Example 2. Controlling Plasmopara viticola in grapevines according to some embodiments of the invention.
Pest organisms
Treatments were duplicated to infect with 2 strains of Plasmopara viticola, consisting of a CAA sensitive strain (A) and a CAA resistant strain (B), in particular resistance to valifenalate.
The strains were multiplied on untreated leaves of 8 days before infection in order to produce enough inoculum to a correct contamination. During these replication steps and before the trial, the sensitivity to the valifenalate was evaluated to validate the sensitivity profile of the strain. Genetic analysis was also carried out to confirm the resistant and sensitive profile of these strains. Half of the crop plants were infected with strain A, while the other half of the crop plants were infected with strain B.
Crop plants
The tests were carried out on young Cabernet sauvignon plants. They were produced in a greenhouse, in a temperature of between 18 and 30 °C from one-eye shoots. These plants were grown in a greenhouse under conditions that ensure control of the quality of the plants and their health status during their cultivation. Homogeneous sets of 6 plants were constituted for the study of each trial condition. A total of 60 plants was required to study all the conditions.
Treatments
According to the experimental design, application mode was a spraying of fungicide on whole plant. Both upper and lower surfaces of the leaves were treated.
A classical application method by spraying was used: the plants were placed in a spray booth equipped with a spray bench carrying 5 nozzles (2 lateral right, 2 lateral left and 1 upper). This bench moves on a guidance rail at a constant speed. The spraying begins from the moment is initiated and before to reach the first plant in order to treat all plants of the same set simultaneously and homogeneously. The pressure at which spraying is applied and the speed of the bench are a function of the volume to be supplied. In this example, the volume of water used was 600 L/ha. The treatments, in particular their composition and application dosage, are summarized in Table 4.
Table 4. Overview of treatments. Conduction of trials
The suspensions of sporocystes of Plasmopara viticola were prepared by washing infected leaves with demineralized water at low temperature in order to block the release of zoospores. The sporulations of the fungus were thus harvested and the spore suspension was then titrated with a Malassez cell. The optimal concentration is 50000 spores/mL. Two suspensions of sporocystes were prepared, on one hand, a suspension with the sensitive strain and, on the other hand, a suspension with the resistant strain. The plants were inoculated by spraying a sporangial suspension on the lower surface of the leaves. Each plant was treated separately and contaminated on each leaf stage. On average, 10 mL was necessary for the contamination of 6 levels of leaves.
After their contamination, the plants were gathered (separating CAA sensitive and CAA resistant inoculated plants) inside a hermetic enclosure so as to maintain a saturated relative humidity, necessary for the development of the disease. Conditions were as follows: a temperature of between 21 and 22 °C, a humidity of 100 %, and a light/dark schedule of 14h/10h lig ht/dark during 8 consecutive days. At the end of this incubation period, the severity of the disease was assessed on each plant and on leaves.
For each plant, an attack rate is determined by visually assessing the infected leaf surface. Then, for each condition of the test (CAA resistant vs. CAA sensitive), a mean attack rate is calculated by averaging the attack rates obtained for the plants of the same condition. From this mean attack rate, the efficacy of the product for each condition can be calculated by comparison to the mean attack rate obtained in the control condition (untreated plants) according to the formula: Efficacy = 100 x [(T - c) / T]; wherein T is the mean attack rate obtained for the control condition (untreated plants) and c is the mean attack rate for treated plants.
Synergistic effect was calculated according to the Colby formula as described, wherein results lower or higher than 1 show antagonism or synergism respectively.
Results
The test results of Example 2 are shown in Tables 5 and 6. Table 5. Test results regarding the control of Plasmopara viticola (strain A, CAA sensitive) in grapevine according to some embodiments of the invention.
Table 6. Test results regarding the control of Plasmopara viticola (strain B, CAA resistant) in grapevine according to some embodiments of the invention.
From these results, it is clearly shown that for the CAA sensitive strain of Plasmopara viticola, the mere combination of valifenalate and cyazofamid in e.g. a tank mix, may have a slightly synergistic effect. Upon treatment with a composition according to the invention however, the synergistic effect is found to be much improved. This shows that compositions of the invention are broadly applicable to organisms in the class of oomycetes. In CAA resistant strains of Plasmopara viticola, efficacy of valifenalate and cyazofamid in a tank mix of the separate formulations was found to be merely additive, while treatment with a composition according to the invention showed a clear synergistic effect. This clearly shows the improved efficacy of compositions of the invention, even when CAA resistant strains are targeted. Example 3. Inducing plant defense pathways in potato according to some embodiments of the invention. Crop plants
The tests were carried out on potato (Bintje variety) in a greenhouse environment. Potato cuttings were made from the apex of a leaf mass. The plants were grown in pots in potting soil. Treatments
Compositions were sprayed on potato leaves carried out up to the runoff limit at the 4th leaf stage. Compositions were applied twice, 4 days apart, in order to maximize the potential expression of defense genes. The dose of the different compositions are presented in Tables 7 and 8.
Table 7. Overview of treatments in Trial 1.
Table 8. Overview of treatments in Trial 2.
Assessment of mode of action with qPFD®
Samples were taken on leaves from three plants of three pots, and bulked in a tube for analysis (technical replicates). For each date, samples were taken from different plants. Samples were collected at 24 hours (24H) and 72 hours (72H), and right after treatments (DO). Analysis tubes with root samples were immediately immerged in liquid nitrogen after sampling to prevent RIMA degradation and then kept at -80°C before processing.
RNAs were extracted using the Macherey Nagel Nucleospin® RNA Plant Kit and a DNAse treatment was performed during extraction, according to the supplier's instructions. For each sample, an RNA quantification and quality control was performed. A reverse transcription (RT) step was then performed on the standardized RNAs.
The qPFD® microarray (WO/2011/161388, Brisset MN, INRA IRHS) is a molecular diagnostic tool measuring the level of expression of plant defense genes by qPCR (Quantitative Polymerase Chain Reaction) at a given time. The targeted genes are involved in defense mechanisms of the following three main classes: chemical barriers, physical barriers and hormonal signaling. The level of expression of these genes provides information on the state of stimulation of the defenses of the plants analyzed.
Each sample was analyzed using 24 defense genes and 3 reference genes (TuA, Actin, GAPDH) of the qPFD® microarray.
The results of the qPFD® were evaluated according to the 2-AACT method which provides the relative expressions of the defense genes in a given sample compared to a control sample (calibrator), expressions normalized by the geometric mean of the 3 reference genes (TuA, Actin, GAPDH) of this sample. The gene expression profiles are visualized in the form of a density map, called Heatmap.
The overexpression or repression of plant defense genes were considered significant above a threshold of >2 or <-2 respectively.
Results
Trial 1 Table 9. Heatmap of the relative expressions of potato qPFD® 28 defense genes in
Trial 1 after 24 hours.
Table 10. Heatmap of the relative expressions of potato qPFD® 28 defense genes in
Trial 1 after 72 hours. No significant plant defense stimulation (PDS) effect was demonstrated 24h after treatment, except for gene PR14 with treatment 4 according to the invention.
On the other hand, 72h after treatment, treatment 4 according to the invention exhibited the strongest defense-stimulating effect, eliciting 8 genes on different defense pathways (PR protein pathway, phenylpropanoid pathway, oxidative stress pathway, salicylic acid pathway and jasmonic acid pathway). Treatments 2, 3 and 5 had little or no effect on the defense genes tested at 72h. Trial 2
Table 11. Heatmap of the relative expressions of potato qPFD® 28 defense genes in
Trial 2 after 24 hours.
Table 12. Heatmap of the relative expressions of potato qPFD® 28 defense genes in Trial 2 after 72 hours.
No significant PDS effect was observed for treatment 2 (valifenalate solo).
Regarding treatment 3 (tank mix of valifenalate and cyazofamid), a significant PDS effect was observed 24h after treatment, for 4 genes. But no PDS effect was observed 72h after treatment. Treatment 4 (composition comprising valifenalate and cyazofamid according to the invention) shows a higher PDS effect, with a larger number of genes (9 genes) 24 after treatment and still 3 genes 72h after treatment.

Claims

1. A method of controlling pests, said method comprising: providing a composition comprising valifenalate and cyazofamid, and applying said composition to a crop plant, a pest population associated with a crop plant, a habitat of a crop plant, or a combination thereof, characterized in that, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1 :5, and wherein said pest population comprises at least one organism chosen from the group of oomycetes.
2. The method according to claim 1, characterized in that, said pest population comprises at least one organism chosen from the group of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
3. The method according to claim 1 or 2, characterized in that, said pest population comprises at least one organism chosen from the group of Phytophthora infestans, Phytophthora capsica, Phytophthora sojae, Phytophthora ramorum, Phytophthora cinnamon, Plasmopara viticola, Bremia lactucae, Pseudoperonospara cubensis, Peronospora farinose, Peronospora sparsa, or combinations thereof.
4. The method according to any one of preceding claims 1-3, characterized in that, said pest population comprises at least one strain which is carboxylic acid amide (CAA) resistant.
5. The method according to any one of preceding claims 1-4, characterized in that, said pest population has a resistance factor (RF) towards at least one carboxylic acid amide (CAA) fungicide of at least 10.
6. The method according to claim 5, wherein said carboxylic acid amide (CAA) fungicide is chosen from the group of valifenalate, dimethomorph, flumorph, pyrimorph, benthiavalicarb, iprovalicarb, mandipropamid, or combinations thereof.
7. The method according to any one of preceding claims 1-6, characterized in that, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 3: 1 and 1 : 1.
8. The method according to any one of preceding claims 1-7, characterized in that, said composition comprises: from 10 to 50 wt.% of valifenalate, and from 5 to 25 wt.% of cyazofamid, based on the total weight of the composition.
9. The composition according to any one of preceding claims 1-8, characterized in that, said composition is formulated as a suspension concentrate (SC), an oil dispersion (OD), as a water dispersible granules (WG), as an emulsifiable concentrate (EC), as a concentrated oil-in-water emulsion (EW) as a wettable powder (WP), as a micro-emulsion (ME), as a capsule suspension (CS), as a suspoemulsion (SE), or as a mixed formulation of CS and SC (ZC).
10. The method according to claim 9, characterized in that, said composition is formulated as a suspension concentrate (SC).
11. The method according to any one of preceding claims 1-10, characterized in that, applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha.
12. The method according to claim 11, characterized in that, applying said composition comprises applying valifenalate in an amount of between 140 and 160 g Al/ha, and applying cyazofamid in an amount of between 70 and 90 g Al/ha.
13. The method according to any one of preceding claims 1-12, characterized in that, said crop plant is selected from the group of potato crops, tomato crops, (grape)vine crops, cucurbit crops, lettuce crops, ornamental plants, or combinations thereof.
14. A method of improving plant resistance against pests and/or inducing plant defense pathways, said method comprising: providing a composition comprising valifenalate and cyazofamid, and applying said composition to a crop plant, a pest population associated with a crop plant, a habitat of a crop plant, or a combination thereof, characterized in that, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1 : 5, and wherein said pest population comprises at least one organism chosen from the group of oomycetes.
15. The method according to claim 14, characterized in that, improving plant resistance against pests and/or inducing plant defense pathways comprises inducing overexpression of one or more plant defense genes.
16. The method according to claim 14 or 15, characterized in that, improving plant resistance against pests and/or inducing plant defense pathways comprises inducing one or more plant defense pathways chosen from the group consisting of systemic acquired resistance (SAR) pathways, in particular PR protein pathways, phenylpropanoid pathways, oxidative stress pathways, salicylic acid pathways, jasmonic acid pathways, or combinations thereof.
17. The method according to claim 15 or 16, characterized in that, said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR5, PR8, PR14, PR15, PAL, CHS, DFR, ANS, PPO, HMGR, FPPS, Far, CSL, Apox, GST, POX, CalS, Peet, CAD, EDS1, WRKY, Lox2, JAR, ACCO, EIN3, or combinations thereof.
18. The method according to any one of preceding claims 15-17, characterized in that, said plant defense genes are chosen from the group consisting of PR1, PR2, PR4, PR8, GST, POX, EDS1, WRKY, Lox2, or combinations thereof.
19. The method according to any one of preceding claims 14-18, characterized in that, said method comprises observing a defense response lasting for at least 72 hours after applying said composition.
20. The method according to any one of preceding claims 14-19, characterized in that, said method comprises inducing said plant defense pathways in the absence of pathogens or additional stimuli.
21. The method according to any one of preceding claims 14-20, characterized in that, said pest population comprises at least one organism chosen from the group of Phytophthora, Plasmopara, Bremia, Pseudoperonospora, Peronospora, or combinations thereof.
22. The method according to any one of preceding claims 14-21, characterized in that, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 3: 1 and 1 : 1.
23. The method according to any one of preceding claims 14-22, characterized in that, said composition comprises: from 10 to 50 wt.% of valifenalate, and from 5 to 25 wt.% of cyazofamid, based on the total weight of the composition.
24. The method according to any one of preceding claims 14-23, characterized in that, said composition is formulated as a suspension concentrate (SC), an oil dispersion (OD), as a water dispersible granules (WG), as an emulsifiable concentrate (EC), as a concentrated oil-in-water emulsion (EW) as a wettable powder (WP), as a micro-emulsion (ME), as a capsule suspension (CS), as a suspoemulsion (SE), or as a mixed formulation of CS and SC (ZC).
25. The method according to any one of preceding claims 14-24, characterized in that, applying said composition comprises applying valifenalate in an amount of between 100 and 200 g Al/ha, and applying cyazofamid in an amount of between 50 and 120 g Al/ha.
26. The method according to any one of preceding claims 14-25, characterized in that, said crop plant is selected from the group of potato crops, tomato crops, (grape)vine crops, cucurbit crops, lettuce crops, ornamental plants, or combinations thereof.
27. A fungicide composition comprising valifenalate and cyazofamid, characterized in that, said valifenalate and said cyazofamid are present in said composition according to a ratio of between 10: 1 and 1 :5.
28. A fungicide composition according to claim 27, for use in a method according to any one of claims 1-13.
29. A fungicide composition according to claim 27, for use in a method according to any one of claims 14-26.
PCT/EP2025/066929 2024-06-17 2025-06-17 Method of controlling pests with a composition comprising valifenalate and cyazofamid Pending WO2025262056A1 (en)

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