DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 2, 4-12 and 16-25 are rejected under 35 U.S.C. 103 as being unpatentable over EP 3 360 415 A1 to Nishimura (“Nishimura”, of record), further in view of US 20190082695 A1 to Gewehr et al. (“Gewehr”), and US 20150264927 A1 to Cristau et al. (“Cristau”).
Nishimura discloses the combination of a DHODH inhibitor of formula (I), including ipflufenoquin (compound a-5, formula 13, page 17; claim 6),
PNG
media_image1.png
271
397
media_image1.png
Greyscale
and a second fungicide, including mandestrobin, isofetamid, metyltetrapol, isofetamid, triflumizole (claims, e.g. claims 1 and 8; the listed second fungicide compounds are respiratory chain inhibitors according to Applicant’s claims 10-12 and 23-25) that provides excellent fungicidal effect against resistant fungi ([0094]). The fungi include, e.g. Zymoseptoria tritici (Septoria tritici; [0077], per Applicant’s claims 6, 7, 19 and 20). The crops include e.g. wheat, barley, rice ([0077- 0079], per Applicant’s claims 8, 9, 21 and 22).
Nishimura discloses that the combination provides excellent fungicidal effect against resistant fungi, but does not explicitly disclose what mutations the resistance is due to.
Gewehr relates to the use of a 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one (herein also referred to as compound I) for combating phytopathogenic fungi on cereals, such fungi containing a mutation in the mitochondrial cytochrome b gene conferring resistance to Qo inhibitors, wherein the mutation is G143A or F129L. ([0001]). It is noted that 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3-methyl-phenyl]-4-methyl-tetrazol-5-one is the chemical name for metyltetrapol, and that this is a second fungicide, per Nishimura, and a second fungicide, per Applicant’s claims as well. Gewehr, also claims as suitable in mixture other second claimed fungicides, as per Nishimura and Applicant’s claims, e.g. mandestrobin. ([0019]). Listed useful crops are e.g. wheat, barley, etc., e.g. for treatment of resistant Septoria tritici (leaf blotch) on wheat. ([0024, [0029]). [0034]).
Gewehr also explains the issue of resistance, namely that: “Qo inhibitor fungicides, often referred to as strobilurin-type fungicides . . . , are conventionally used to control a number of fungal pathogens in crops. Qo inhibitors typically work by inhibiting respiration by binding to a ubihydroquinone oxidation center of a cytochrome bc.sub.1 complex (electron transport complex III) in mitochondria . . . Unfortunately, widespread use of such Qo inhibitors has resulted in the selection of mutant pathogens which are resistant to such Qo inhibitors . . . Resistance to Qo inhibitors has been detected in several phytopathogenic fungi. In some pathogens, the major part of resistance to Qo inhibitors in agricultural uses has been attributed to pathogens containing a single amino acid residue substitution G143A in the cytochrome b gene for their cytochrome bc.sub.1 complex, the target protein of Qo inhibitors . . . whereas in other pathogens a substitution of F129L confers resistant to Qo inhibitors.” ([0002]).
Based on the above, Gewehr concludes that new methods and compositions are desirable for controlling these pathogen induced diseases in crops comprising plants subjected to pathogens that are resistant to Qo inhibitors, namely compounds having improved activity and/or a broader activity spectrum against such resistant phytopathogenic harmful fungi on cereal plants, as well as mixtures of compounds of methyltetrapol with second compounds, such as mandestrobin, etc. ([0014], [0019]).
Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to combine the teachings of Nishimura and Gewehr in order to practice Applicant’s claimed invention of claims 1, 2 and 4-12 with a reasonable expectation of success. The skilled artisan would have been motivated to do so because Nishimura claims a combination of Applicant’s claimed compounds are useful for the treatment of resistant fungi. Further motivation to do so is found in view of Gewehr, which specifically discloses resistance due to mitochondrial cytochrome b gene conferring resistance to Qo inhibitors, wherein the mutation is G143A or F129L, and specifically discloses the use of a number of respiratory chain inhibitors of Applicant’s claims as useful for the treatment of such mutations. Gewehr further discloses that mixing of compounds is further useful in providing a broader spectrum of activity and overcoming resistance. Accordingly, it would have been obvious to a person of skill in the art to apply a mixture of compounds, as taught by Nishimura, for achieving an enhanced anti-fungal effect on crops infected by fungi with resistance and mutations in the G143A or F129L genes.
Cristau relates to the use of N-cyclopropyl-N-[substituted-benzyl]-3-(difluoromethyl)-5-fluoro-1-methyl- -1H-pyrazole-4-carboxamide or thiocarboxamide derivatives and/or salts thereof for improving growth in crops, comprising preventively and/or curatively controlling resistant strains of fungi, particularly for controlling strains of fungi resistant to SDHI fungicides. (Abstract). The compounds are used for treating plants curatively and/or preventively against at least one resistant strain of fungi which is resistant to at least one SDHI (succinate dehydrogenase inhibitor) fungicide. ([0033]).
Table 2 lists specific mutations responsible for the resistance, such as “Ustilago maydis B-H257L Mycosphaerella graminicola B-H267Y/R/L; B-I269V; C-H152R; C-N86K; D-H139E and many others Aspergillus oryzae B-H249Y/L/N; C-T90I; D-D124E Botrytis cinerea B-P225L/T/F; B-H272Y/R/L; B-N230I; D-H132R Botrytis elliptica B-H272Y/R Alternaria alternata B-H277Y/R; C-H134R; D-D123E; D-H133R Corynespora cassiicola B-H287Y/R; C-S73P; D-S89P Didymella bryoniae B-H277R/Y Podosphaera xanthii B-H->Y Sclerotinia sclerotiorum D-H132R Stemphylium botryose B-P225L; H272Y/R.” This discloses overlapping mutations and fungi with Applicant’s claims. Cristau discloses involvement of e.g. the SDHB gene. ([0177]). Among the plants, which can be protected include e.g. wheat, rice, barley, etc. ([0061]).
Per Cristau, inhibitors of the respiratory chain at complex III, include for example (3.1) ametoctradin, (3.2) amisulbrom, (3.3) azoxystrobin, (3.4) cyazofamid, (2E)-2-(methoxyimino)-N-methyl-2-{2-[(E)-({1-[3-(trifluoromethyl)phenyl]e- thoxy}imino)methyl]phenyl}acetamide, (3.26) (2E)-2-{2-[({[(1E)-1-(3-{[(E)-1-fluoro-2-phenylvinyl]oxy}phenyl)ethyliden- e]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylacetamide. ([0056]). This discloses multiple overlapping compounds with Applicant’s claims.
Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to combine the teachings of Nishimura and Cristau in order to practice Applicant’s claimed invention of claims 16-25 with a reasonable expectation of success. The skilled artisan would have been motivated to do so because Nishimura claims a combination of Applicant’s claimed compounds are useful for the treatment of resistant fungi. Further motivation to do so is found in view of Cristau, which specifically discloses conferring resistance to SDHI fungicides, with involvement of e.g. the SDHB gene, and with multiple specific known mutations associated with it, and which further specifically discloses the use of multiple overlapping inhibitors of Applicant’s claims as useful for the treatment of such mutations. Cristau further discloses that mixing of compounds is further useful in providing a broader spectrum of activity and overcoming resistance. Accordingly, it would have been obvious to a person of skill in the art to apply a mixture of compounds, as taught by Nishimura, for achieving an enhanced anti-fungal effect on crops infected by fungi with resistance and mutations in the SDH genes.
Other relevant art
The Examiner also notes for the record the following relevant art over which no rejections were made solely in view of its cumulative nature.
D2 WO 2020/120204 A2 (BASF AGRO BV [NL]) 18 June 2020
D3 WO 2018/050421 A1 (BASF SE [DE]) 22 March 2018
D4 US 2020/352168 A1 (WATANABE SHINYA [JP]) 12 November 2020
D5 WO 2018/089237 A1 (DOW AGROSCIENCES LLC [US]) 17 May 2018
D2 similarly discloses the control of S. tritici that are resistant to fungicides, in particular azole fungicides, using a combination of mefentrifluconazole and a second fungicide, including ipflufenoquin (II-10) and quinofunelin (II-14; claims).
PNG
media_image2.png
113
430
media_image2.png
Greyscale
D3 also discloses a fungicidal mixture of ipflufenoquin (compound I-2) and a further selected fungicide for control of resistant fungi (page 2, lines 12-20), including Septoria tritici (page 6, line 6), albeit from a long list.
PNG
media_image3.png
93
422
media_image3.png
Greyscale
D4 discloses phenoxy quinoline compounds, including ipflufenoquin (compound a-1, page 1) and teaches that the compounds provide excellent control of resistant fungi (paragraph 99) and are preferably applied to control inter alia from a short list, Septoria leaf spot of wheat (paragraph 100).
PNG
media_image4.png
112
466
media_image4.png
Greyscale
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SVETLANA M IVANOVA/ Primary Examiner, Art Unit 1627
Prosecution Insights