't IA
`D'
`Igl a
`(DAS)
`
`_
`S
`66655 el‘Vlce
`
`WIPO
`
`WORLD
`INTELLECTUAL PROPERTY
`ORGANIZATION
`
`CERTIFICATE OF AVAILABILITY OF A CERTIFIED PATENT DOCUMENT IN A
`
`DIGITAL LIBRARY
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`The International Bureau certifies that a copy of the patent application indicated
`below has been available to the WIPO Digital Access Service since the date of
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`Document details:
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`Country/Office: G B
`
`Filing date:
`
`01 Jun 2016 (01.06.2016)
`
`Application number: 16095747
`
`Date of availability of document:
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`13 Jul 2016 (13.07.2016)
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`JP, US, SE, NZ, KR, GB, AU, ES, IB, EE, CN, MA, Fl
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`Concept House
`Cardiff Road
`
`Newport
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`
`NP 1 0 8QQ
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`Certified Office Copy
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`1, the undersigned, being an officer duly authorised in accordance with Section 74(1) and (4) of the
`Deregulation & Contracting Out Act 1994, to sign and issue certificates on behalf of the
`Comptroller-General, hereby certify that annexed hereto is a true copy of the documents as originally
`filed in connection with patent application GB1609574.7 filed on 01 June 2016, and as stored
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`Signed A HAYES
`
`Dated
`
`06 June 2016
`
`

`

`.
`
`.~§
`
` _
`Intellectual
`
`Property
`OffiCe
`
`Patents Form 1
`Patents Act 1977 (Rule 12)
`
`Request for grant of a patent
`
`1200196441
`1016012307 D02093
`01/06/2016 150.00 DepositAccount
`
`Concept House
`Cardiff Road
`Newport
`South Wales
`NP10 SQQ
`
`Application number
`1. Your reference
`
`GB 16095747
`
`2.
`
`Full name, address and postcode of the applicant or of
`each applicant
`
`Patents ADP number (if you know it)
`3. Title of the invention
`
`4. Name of your agent (ifyou have one)
`“Address for sen/ice" to which all correspondence should
`be sent. This may be in the European Economic area or
`Channel Islands (see warning note below)
`(including the postcode)
`
`Patents ADP number (if you know it)
`
`5. Priority declaration: Are you claiming priority from one or
`more earlier-filed patent applications? If so, please give
`details ofthe application(s)
`
`81047-GB-NAT-1
`
`SYNGENTA PARTICIPATIONS AG
`Schwarzwaldallee 215
`Basel 4058
`Switzerland
`
`FUNGICIDAL COMPOSITIONS
`
`PALMER, Sarah Louise
`PALMER, Sarah Louise
`PO Box 3538
`Syngenta Limited
`Intellectual Property Department
`Jealott's Hill International Research Centre
`Bracknell RG42 6YA
`Berkshire
`
`United Kingdom
`
`Country
`
`Application number
`
`Date of filing
`
`PDAS Access Code
`
`Number of earlier UK
`application
`
`Date of filing
`(day/ month / year)
`
`6. Divisionals etc: Is this application a divisional application,
`or being made following resolution of an entitlement
`dispute about an earlier application. If so, please give the
`application number and filing date ofthe earlier
`application
`
`7.
`
`lnventorship: (Inventors must be individuals not
`companies)
`
`Are all the applicants named above also inventors?
`
`8. Are you paying the application fee with this form?
`
`No
`
`Yes
`
`(REV DEC07)
`Intellectual Property Office is an operating name ofthe Patent Office
`
`Patents Form 1(e)
`https://www.gov.uk/ipo
`
`

`

`Patents Form 1
`
`9. Accompanying documents: please enterthe number of
`pages of each item accompanying this form.
`
`Continuation sheets of this form
`
`Description:
`
`24
`
`Claim(s):
`
`Abstract:
`
`3
`
`1
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`Drawing(s):
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`n/a
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`If you are n_ot filing a description, please give details of
`the previous application you are going to rely upon
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`10. If you are also filing any of the following, state how many
`against each item.
`
`Priority documents:
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`Statement of inventorship and right to grant of a patent
`(Patents Form 7):
`
`Request for search (Patents Form 9A):
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`0
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`0
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`Pre-conversion Archive
`Any other documents (please specify):
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`PDAS Registration Form
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`11. WVe request the grant of a patent on the basis of this application.
`
`Signature: Subject: Sarah Palmer 27345; Issuer:
`European Patent Office, European Patent
`Office CA GZ
`
`Date:
`
`01 Jun 2016
`
`12. Name, e-mail address, telephone, fax and/or mobile
`number, if any, of a contact point for the applicant
`Warning
`After an application for a patent has been filed, the Comptroller will consider whether publication or communication of the
`invention should be prohibited or restricted under section 22 of the Patents Act 1977. You will be informed if it is necessary to
`prohibit or restrict your invention in this way. Furthermore, if you are resident in the United Kingdom and your application contains
`information which relates to military technology, or would be prejudicial to national security orthe safety of the public, section 23 of
`the Patents Act 1977 prohibits you from applying for a patent abroad without first getting written permission from the Office unless
`an application has been filed at least 6 weeks beforehand in the United Kingdom for a patent for the same invention and either no
`direction prohibiting publication or communication has been given, or any such direction has been revoked. Until such time or until
`the revocation of any direction, for any such application the address for service referred to at part 4 above must be in the United
`Kingdom.
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`Although you may have an address for service in the Channel Islands, any agent instructed to act for you must reside or have a
`place of business in the European Economic Area or Isle of Man.
`
`(REV DECO7)
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`Patents Form 1(e)
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 1 -
`
`FUNGICIDAL COMPOSITIONS
`
`The present invention relates to novel fungicidal compositions for the treatment of
`
`phytopathogenic diseases of useful plants, especially phytopathogenic fungi, and to a
`
`method of controlling such diseases, and/or fungi, on useful plants.
`
`It is known from W02008/148570, WO 2010/063700, WO 2010/084078 and WO
`
`2008/151828 that certain pyrazonI-carboxamide derivatives have biological activity against
`
`phytopathogenic fungi. On the other hand various fungicidal compounds of different memical
`
`classes are widely known as plant fungicides for application in various crops of cultivated
`
`10
`
`15
`
`plants. However, crop tolerance and activity against phytopathogenic plant fungi do not
`
`always satisfy the needs of agricultural practice in many incidents and aspects. In order to
`
`overcome this problem, some binary mixtures of pyrazolyl—carboxamides with certain
`
`fungicides have been provided in WO 2012/041874, and WO 2015/049178.
`
`Fungicidal pyridazine derivatives are disclosed in EP1767529A1, and binary m'xtures
`
`of such compounds with Qol inhibitors are disclosed in EP2604116A1.
`
`The present invention provides a composition suitable for control of diseases caused
`
`by phytopathogens comprising, as component (A), a compound of formula (I)
`
`(I),
`
`20
`
`wherein
`
`R is hydrogen or methoxy;
`
`Q is
`
`(Q2);
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 2 -
`
`wherein
`
`R1 is hydrogen, halogen or C1-C6alkyl;
`
`R2 is hydrogen, halogen, Cq-Cealkyl, Cz-Csalkenyl, Cs-Cealkinyl, Cs-Cscycloalkyl-Cs-
`
`Csalkinyl, halophenoxy, halophenyl—Cs—Csalkinyl, C(C1—C4alkyl)=NO—01—C4alkyl, C1-
`
`Cehaloalkyl,
`
`C1-Cshaloalkoxy, Cz-Cshaloalkenyl, or Cz-Cshaloalkenyloxy;
`
`R3 is hydrogen, halogen or C1-C6alkyl; with the proviso that at least one of R1, R2 and
`
`R3 is different from hydrogen;
`
`R4, R5 and Rs, independently from each other, are hydrogen, halogen or -E-R7; with
`
`the proviso that at least one of R4, R5 and R6 is different from hydrogen;
`
`R7 is hydrogen, Cq-Cealkyl, Cq-Cehaloalkyl or Cq-C4alkoxyalkyl; and
`
`R8 is hydrogen or methoxy;
`
`and agrochemically acceptable salts, stereoisomers, diastereoisomers, enantiomers
`
`and tautomers of those compounds;
`
`and as component (B), a compound of formula (II)
`
`
`
`(II) or an agrochemically acceptable salt thereof, wherein,
`
`R21 is hydrogen or halogen;
`
`R22, R23 and R24 are each independently hydrogen or halogen; and,
`
`R25 is halogen or cyano.
`
`In a further aspect, the invention provides a method of controlling phytopathogenic
`
`diseases on useful plants or on propagation material thereof, which comprises applying to
`
`the useful plants, the locus thereof or propagation material thereof a combination of
`
`components (A) and (B) as described herein.
`
`The compounds of formula (I) wherein R8 is hydrogen can occur in the two
`
`enantiomeric forms of formula (la) and (lb):
`
`10
`
`15
`
`20
`
`25
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 3 -
`
`F
`
`F
`
`H
`
`o
`
`/
`N\
`
`\
`
`l“
`C H3
`
`33
`
`Q
`
`H
`
`N\R
`
`R8
`
`F
`
`(la) and
`
`H 3C
`
`H
`
`’—
`N\
`
`R
`
`H
`
`O
`Ra
`
`(lb).
`
`F
`
`o
`
`H
`
`\
`
`N/
`\N|
`CH3
`
`The invention encompasses both enantiomeric forms of the compounds of formula (I).
`
`The compounds of formula (I) and their preparation are described in WO 2010/063700, WO
`
`2010/084078 and WO 2008/151828.
`
`Compounds of formula (II) and their preparation are described in EP1767529A, and
`
`EP2604116A1.
`
`It has been found that the use of a compound of formula (II) in combination with a
`
`compound of formula (I) surprisingly and substantially may enhance the effectiveness of the
`
`latter against fungi, and vice versa. Additionally, the method of the invention is effective
`
`against a wider spectrum of such fungi than can be combated with the individual active
`
`ingredients, when used solely.
`
`In general, the weight ratio of component (A) to component (B) is from 1000:1 to
`
`1:1000, especially from 50:1 to 1:50, more especially in a ratio from 40:1 to 1:40, even more
`
`especially in a ratio of from 20:1 to 1:20, even more especially still from 10:1 to 1:10, and
`
`very especially from 5:1 and 1:5. Special preference is given to a ratio of from 2:1 to 1:2, and
`
`a ratio of from 4:1 to 2:1 is also especially preferred. Specific individual ratios that are
`
`preferred include the ratio of 1:1, 5:1, 5:2, 5:3, 5:4, 4:1, 4:2, 4:3, 3:1, 3:2, 2:1, 1:5, 2:5, 3:5,
`
`4:5, 1:4, 2:4, 3:4, 1:3, 2:3, 1:2, 1:600, 1:300, 1:150, 1:100, 1:50, 1;40, 1:35, 1:20, 2:35, 4:35,
`
`1:10 1:75, 2:75, 4:75, 1:6000, 1:3000, 1:1500, 1:350, 2:350, 4:350, 1:750, 2:750, and 4:750.
`
`It has been found, surprisingly, that certain weight ratios of component (A) to
`
`component (B) are able to give rise to synergistic activity. Therefore, a further aspect of the
`
`invention are compositions, wherein component (A) and component (B) are present in the
`
`composition in amounts producing a synergistic effect. This synergistic activity is apparent
`
`from the fact that the fungicidal activity of the composition comprising component (A) and
`
`component (B) is greater than the sum of the fungicidal activities of component (A) and
`
`component (B). This synergistic activity extends the range of action of component (A) and
`
`component (B) in two ways. Firstly, the rates of application of component (A) and component
`
`(B) are lowered whilst the action remains equally good, meaning that the active ingredient
`
`1O
`
`15
`
`20
`
`25
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 4 -
`
`mixture still achieves a high degree of phytopathogen control even where the two individual
`
`components have become totally ineffective in such a low application rate range. Secondly,
`
`there is a substantial broadening of the spectrum of phytopathogens that can be controlled.
`
`A synergistic effect exists whenever the action of an active ingredient combination is
`
`greater than the sum of the actions of the individual components. The action to be expected
`
`E for a given active ingredient combination obeys the so-called COLBY formula and can be
`
`calculated as follows (COLBY, SR. "Calculating synergistic and antagonistic responses of
`
`herbicide combination", Weeds, Vol. 15, pages 20-22; 1967):
`
`ppm = milligrams of active ingredient (= a.i.) per liter of spray mixture
`
`X = % action by active ingredient (A) using p ppm of active ingredient
`
`Y = % action by active ingredient (B) using q ppm of active ingredient.
`
`According to COLBY, the expected (additive) action of active ingredients (A)+(B) using
`
`p+q ppm of active ingredient is
`
`E = X + Y - %
`
`If the action actually observed (0) is greater than the expected action (E), then the action of
`
`the combination is super—additive, i.e. there is a synergistic effect. In mathematical terms,
`
`synergism corresponds to a positive value for the difference of (O-E). In the case of purely
`
`complementary addition of activities (expected activity), said difference (O-E) is zero. A
`
`negative value of said difference (O-E) signals a loss of activity compared to the expected
`
`activity.
`
`However, besides the actual synergistic action with respect to fungicidal activity, the
`
`compositions according to the invention can also have further surprising advantageous
`
`properties. Examples of such advantageous properties that may be mentioned are: more
`
`advantageuos degradability; improved toxicological and/or ecotoxicological behaviour; or
`
`improved characteristics of the useful plants including: emergence, crop yields, more
`
`developed root system, tillering increase, increase in plant height, bigger leaf blade, less
`
`dead basal leaves, stronger tillers, greener leaf colour, less fertilizers needed, less seeds
`
`needed, more productive tillers, earlier flowering, early grain maturity, less plant verse
`
`(lodging), increased shoot growth, improved plant vigor, and early germination.
`
`Some compositions according to the invention have a systemic action and can be
`
`used as foliar, soil and seed treatment fungicides.
`
`With the compositions according to the invention it is possible to inhibit or destroy the
`
`phytopathogenic microorganisms which occur in plants or in parts of plants (fruit, blossoms,
`
`1O
`
`15
`
`20
`
`25
`
`30
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 5 -
`
`leaves, stems, tubers, roots) in different useful plants, while at the same time the parts of
`
`plants which grow later are also protected from attack by phytopathogenic microorganisms.
`
`The compositions according to the invention can be applied to the phytopathogenic
`
`microorganisms, the useful plants, the locus thereof, the propagation material thereof,
`
`storage goods or technical materials threatened by microorganism attack.
`
`The compositions according to the invention may be applied before or after infection of
`
`the useful plants, the propagation material thereof, storage goods or technical materials by
`
`the microorganisms.
`
`1O
`
`15
`
`20
`
`25
`
`A further aspect of the present invention is a method of controlling diseases on useful
`
`plants or on propagation material thereof caused by phytopathogens, which comprises
`
`applying to the useful plants, the locus thereof or propagation material thereof a composition
`
`according to the invention. Preferred is a method, which comprises applying to the useful
`
`plants or to the locus thereof a composition according to the invention, more preferably to the
`
`useful plants. Further preferred is a method, which comprises applying to the propagation
`
`material of the useful plants a composition according to the invention.
`
`Throughout this document the expression “composition” means the various mixtures or
`
`combinations of components (A) and (B), for example in a single “ready-mix” form, in a
`
`combined spray mixture composed from separate formulations of the single active ingredient
`
`components, such as a “tank—mix”, and in a combined use of the single active ingredients
`
`when applied in a sequential manner, i.e. one after the other with a reasonably short period,
`
`such as a few hours or days. The order of applying the components (A) and (B) is not
`
`essential for working the present invention.
`
`Compounds of formula (I) wherein Q is Q1, are preferred as component A. In particular,
`
`compounds of formula (I) wherein Q is Q, R, R2 and R3 are halogen (more especially
`
`chloro), R is methoxy and R8 is hydrogen are particularly preferred as component A.
`
`Preferred components (A) are listed in Tables 1 & 2 below.
`
`Table 1:
`
`Compounds of formula (lc):
`
`H
`
`(lo),
`
`FH O WQ
`T
`H R8
`OCH3
`
`\
`
`N I
`
`F
`
`30
`
`wherein
`
`I
`\
`
`N
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 6 -
`
`Qis
`
`R1
`
`R3
`
`R2
`
`(Q1) or
`
`R4
`
`\ R5
`\ s
`
`.
`(02),
`
`R6
`
`
`
`Compound No.
`
`R1
`
`R2
`
`R3
`
`R4
`
`R5
`
`R6
`
`R8
`
`Q
`
`Q1
`
`
`
`
`
`
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 7 -
`
`Compound NO- __mE-m-mmm
`___--_---
`
`————-—-——
`
`Table 2: Compounds of formula (Id):
`
`wherein
`Qis
`
`5
`
`H
`
`> SKQ
`N H R8
`
`(Id),
`
`F
`
`FH o
`
`N:
`
`\N
`I
`
`R1
`
`R
`
`R2
`
`(Q1) or
`
`R4
`
`\
`
`R
`
`\ R5
`
`8
`
`(Q2);
`
`DU
`Compound No.
`R1
`R2
`R3
`Q
`
`2.001
`CI
`CI
`CI
`Q1
`II
`2.002
`CI
`H
`CI
`Q1
`———_-———_
`III
`———_-———_
`———_-———_
`———_-———_
`II
`———_-———_
`———_-———_
`II
`___--_---
`
` 2.010 Q2 CI H CI
`
`
`
`---------
`II
`_----_---
`.
`2
`CI
`H
`Br
`
`---------
`
`I I
`I I
`
`___--_---
`2.016
`-
`-
`-
`Q2
`CI
`H
`H
`H
`2.017
`CI
`CI
`CI
`Q1
`-
`-
`-
`OCH3
`2.018
`CI
`H
`CI
`Q1
`-
`-
`-
`OCH3
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 8 -
`
`—— A
`
`
`2.022
`
`2.023
`2.024
`2.025
`
`2.026
`
`particular preferred component (A) is the compound No. 1.001 (3—(difluoromethyl)—N—
`
`methoxy-1-methyl-N-[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]pyrazole-4-carboxamide). Thus,
`
`particularly preferred mixtures comprise as component (A) 3-(difluoromethyl)-N-methoxy-1-
`
`methyl-N-[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]pyrazole-4-carboxamide and a compound
`
`of formula (II).
`
`Particularly preferred components (B) are listed below in Table 3.
`
`10
`
`
`TABLE 3 Compounds of formula (II)
`
`Compou nd
`R21
`R22
`R23
`R24
`R25
`(Ila)
`CI
`
`
`
`Thus disclosed herein are compositions comprising any one of components (A) from
`
`Table 1 in combination with compound (Ila); compositions comprising any one of
`
`components (A) from Table 2 in combination with compound (Ila); compositions comprising
`
`any one of components (A) from Table 1 in combination with compound (llb); compositions
`
`comprising any one of components (A) from Table 2 in combination with compound (llb);
`
`compositions comprising any one of components (A) from Table 1 in combination with
`
`compound (llc); compositions comprising any one of components (A) from Table 2 in
`
`combination with compound (llc); compositions comprising any one of components (A) from
`
`Table 1 in combination with compound (lld); compositions comprising any one of
`
`15
`
`20
`
`

`

`81047—GB—REG—ORG—NAT1
`
`- 9 -
`
`components (A) from Table 2 in combination with compound (Ild); and compositions
`
`comprising any one of components (A) from Table 1 in combination with compound (lle);
`
`compositions comprising any one of components (A) from Table 2 in combination with
`
`compound (lle).
`
`Particularly preferred mixtures comprise as component (A), a compound of formula (I)
`
`(in particular 3-(difluoromethyl)-N-methoxy-1-methyl-N-[‘l-methyl-2-(2,4,6-
`
`trichlorophenyl)ethyl]pyrazole-4-carboxamide) and as component B, any one of the
`
`compounds of formula (II) as listed in Table 3, and in particular any one of compounds (Ila),
`
`(llb), (llc) and (lid).
`
`In one embodiment component A is 3-(difluoromethyl)—N-methoxy-1-methyl-N-[‘l-
`
`methyl-2-(2,4,6-trichlorophenyl)ethyl]pyrazole-4-carboxamide, and component B is 3-chloro-
`
`5-(4-chlorophenyl)—6-methyl-4-(2,4,6—trifluorophenyl)pyridazine.
`
`In another embodiment component A is 3-(difluoromethyl)-N-methoxy-1-methyl-N-[1-
`
`methyl—2—(2,4,6—trichlorophenyl)ethyl]pyrazole-4—carboxamide, and component B is 3—chloro—
`
`6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine.
`
`In a further embodiment component A is 3-(difluoromethyl)—N-methoxy—1-methyl-N-[1-
`
`methyl-2-(2,4,6-trichlorophenyl)ethyl]pyrazole-4-carboxamide, and component B is 4-(2,6—
`
`difluorophenyl)—3-chloro-6-methyl-5-phenyl-pyridazine.
`
`In yet a further embodiment component A is 3—(difluoromethyl)—N—methoxy—1—methyl—N—
`
`[1-methyl-2-(2,4,6-trichlorophenyl)ethyl]pyrazole-4—carboxamide, and component B is 4-(2,6-
`
`difluorophenyl)—6-methyl-5-phenyl-pyridazine-3-carbonitrile.
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`The active ingredient combinations are effective against harmful microorganisms, such
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`as microorganisms, that cause phytopathogenic diseases, in particular against
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`phytopathogenic fungi and bacteria.
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`The active ingredient combinations are effective especially against phytopathogenic
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`fungi belonging to the following classes: Ascomycetes (e.g. Venturia, Podosphaera,
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`Erysiphe, Monilinia, Mycosphaerella, Uncinula); Basidiomycetes (e.g. the genus Hemileia,
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`Rhizoctonia, Phakopsora, Puccinia, Ustilago, Tilletia); Fungi imperfecti (also known as
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`Deuteromycetes; e.g. Botrytis, Helminthosporium, Rhynchosporium, Fusarium, Septoria,
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`Cercospora, Alternaria, Pyricularia and Pseudocercosporella); Oomycetes (e.g.
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`Phytophthora, Peronospora, Pseudoperonospora, Albugo, Bremia, Pythium,
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`Pseudosclerospora, Plasmopara).
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`According to the invention “useful plants” typically comprise the following species of
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`plants: grape vines; cereals, such as wheat, barley, rye or oats; beet, such as sugar beet or
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`fodder beet; fruits, such as pomes, stone fruits or soft fruits, for example apples, pears,
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`plums, peaches, almonds, cherries, strawberries, raspberries or blackberries; leguminous
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`plants, such as beans, lentils, peas or soybeans; oil plants, such as rape, mustard, poppy,
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`olives, sunflowers, coconut, castor oil plants, cocoa beans or groundnuts; cucumber plants,
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`such as marrows, cucumbers or melons; fibre plants, such as cotton, flax, hemp orjute;
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`citrus fruit, such as oranges, lemons, grapefruit or mandarins; vegetables, such as spinach,
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`lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, cucurbits or paprika;
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`lauraceae, such as avocados, cinnamon or camphor; maize; tobacco; nuts; coffee; sugar
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`cane; tea; vines; hops; durian; bananas; natural rubber plants; turf or ornamentals, such as
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`flowers, shrubs, broad-leaved trees or evergreens, for example conifers. This list does not
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`represent any limitation.
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`The term "useful plants" is to be understood as including also useful plants that have
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`been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for
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`example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and
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`trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS
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`(glutamine synthetase) inhibitors) as a result of conventional methods of breeding or genetic
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`engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g.
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`imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape
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`(Canola). Examples of crops that have been rendered tolerant to herbicides or classes of
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`herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant
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`maize varieties commercially available under the trade names RoundupReady® , Herculex l
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`® and LibertyLink®.
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`The term "useful plants" is to be understood as including also useful plants which have
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`been so transformed by the use of recombinant DNA techniques that they are capable of
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`synthesising one or more selectively acting toxins, such as are known, for example, from
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`toxin-producing bacteria, especially those of the genus Bacillus.
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`Toxins that can be expressed by such transgenic plants include, for example,
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`insecticidal proteins, for example insecticidal proteins from Bacillus cereus or Bacillus
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`popliae; or insecticidal proteins from Bacillus thuringiensis, such as 6-endotoxins, e.g.
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`CrylA(b), CrylA(c), CrylF, CrylF(a2), CryllA(b), CrylllA, CrylllB(b1) or Cry9c, or vegetative
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`insecticidal proteins (VIP), e.g. VIP1, VIP2, V|P3 or VlP3A; or insecticidal proteins of bacteria
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`colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as
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`Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such
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`as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins
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`produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley
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`lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsine inhibitors,
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`serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome—inactivating proteins
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`(RIP), such as ricin, maize—RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes,
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`such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol
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`oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers
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`of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors,
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`stilbene synthase, bibenzyl synthase, chitinases and glucanases.
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`In the context of the present invention there are to be understood by 6-endotoxins, for
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`example CrylA(b), CrylA(c), CrylF, CrylF(a2), CryllA(b), CrylllA, CrylllB(b1) or Cry9c, or
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`vegetative insecticidal proteins (VIP), for example VIP1, VIP2, V|P3 or VlP3A, expressly also
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`hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly
`
`by a new combination of different domains of those proteins (see, for example, WO
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`02/15701). An example for a truncated toxin is a truncated CrylA(b), which is expressed in
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`the Bt11 maize from Syngenta Seed SAS, as described below. In the case of modified
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`toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino
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`acid replacements, preferably non—naturally present protease recognition sequences are
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`inserted into the toxin, such as, for example, in the case of CrylllA055, a cathepsin-D-
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`recognition sequence is inserted into a CrylllA toxin (see WO 03/018810)
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`Examples of such toxins or transgenic plants capable of synthesising such toxins are
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`disclosed, for example, in EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529,
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`EP—A—451 878 and WO 03/052073.
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`The processes for the preparation of such transgenic plants are generally known to the
`
`person skilled in the art and are described, for example, in the publications mentioned above.
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`Cryl-type deoxyribonucleic acids and their preparation are known, for example, from WO
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`95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.
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`The toxin contained in the transgenic plants imparts to the plants tolerance to harmful
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`insects. Such insects can occur in any taxonomic group of insects, but are especially
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`commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies
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`(Lepidoptera).
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`Transgenic plants containing one or more genes that code for an insecticidal resistance
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`and express one or more toxins are known and some of them are commercially available.
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`Examples of such plants are: YieldGard® (maize variety that expresses a CrylA(b) toxin);
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`YieldGard Rootworm® (maize variety that expresses a CrylllB(b1) toxin); YieldGard Plus®
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`(maize variety that expresses a CrylA(b) and a Cryll|B(b1) toxin); Starlink® (maize variety
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`that expresses a Cry9(c) toxin); Herculex l® (maize variety that expresses a CrylF(a2) toxin
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`and the enzyme phosphinothricine N—acetyltransferase (PAT) to achieve tolerance to the
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`herbicide glufosinate ammonium); NuCOTN 33B® (cotton variety that expresses a CrylA(c)
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`toxin); Bollgard l® (cotton variety that expresses a CrylA(c) toxin); Bollgard ll® (cotton variety
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`that expresses a CrylA(c) and a CryllA(b) toxin); VIPCOT® (cotton variety that expresses a
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`VIP toxin); NewLeaf® (potato variety that expresses a CrylllA toxin); NatureGard® and
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`Protecta®.
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`Further examples of such transgenic crops are:
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`1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur,
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`France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been
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`rendered resistant to attack by the European corn borer (Ostrinia nubile/is and Sesamia
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`nonagrioides) by transgenic expression of a truncated CrylA(b) toxin. Bt1 1 maize also
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`transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate
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`ammonium.
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`2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St.
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`Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which
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`has been rendered resistant to attack by the European corn borer (Ostrinia nubile/is and
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`Sesamia nonagrioides) by transgenic expression of a CrylA(b) toxin. Bt176 maize also
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`transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate
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`ammonium.
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`3. M|R604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St.
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`Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered
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`insect—resistant by transgenic expression of a modified CrylllA toxin. This toxin is Cry3A055
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`modified by insertion of a cathepsin-D-protease recognition sequence. The preparation of
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`such transgenic maize plants is described in WC 03/018810.
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`4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150
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`Brussels, Belgium, registration number C/DE/O2/9. MON 863 expresses a Cryll|B(b1) toxin
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`and has resistance to certain Coleoptera insects.
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`5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150
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`Brussels, Belgium, registration number C/ES/96/02.
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`6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160
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`Brussels, Belgium, registration number C/NL/OO/10. Genetically modified maize for the
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`expression of the protein Cry1 F for achieving resistance to certain Lepidoptera insects and of
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`the PAT protein for achieving tolerance to the herbicide glufosinate ammonium.
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`7. NK603 x MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de
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`Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of
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`conventionally bred hybrid maize varieties by crossing the genetically modified varieties
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`NK603 and MON 810. NK603 x MON 810 Maize transgenically expresses the protein CP4
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`EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the
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`herbicide Roundup® (contains glyphosate), and also a CrylA(b) toxin obtained from Bacillus
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`thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the
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`European corn borer.
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`Transgenic crops of insect-resistant plants are also described in BATS (Zentrum fUr
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`Biosicherheit und Nachhaltigkeit, Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland)
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`Report 2003, (http://bats.ch).
`
`The term "useful plants" is to be understood as including also useful plants which have
`
`been so transformed by the use of recombinant DNA techniques that they are capable of
`
`synthesising antipathogenic substances having a selective action, such as, for example, the
`
`so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of
`
`such antipathogenic substances and transgenic plants capable of synthesising such
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`antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818,
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`and EP—A—0 353 191. The methods of producing such transgenic plants are generally known
`
`to the person skilled in the art and are described, for example, in the publications mentioned
`
`above.
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`Antipathogenic substances which can be expressed by such transgenic plants include,
`
`for example, ion channel blockers, such as blockers for sodium and calcium channels, for
`
`example the viral KP1, KP4 or KP6 toxins; stilbene synthases; bibenzyl synthases;
`
`chitinases; glucanases; the so-called "pathogenesis-related proteins" (PRPs; see e.g. EP-A-0
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`392 225); antipathogenic substances produced by microorganisms, for example peptide
`
`antibiotics or heterocyclic antibiotics (see e.g. WO 95/33818) or protein or polypeptide factors
`
`involved in plant pathogen defence (so-called "plant disease resistance genes", as described
`
`in WC 03/000906).
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`Useful plants of elevated interest in connection with present in