(I 2) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property Organization
`International Bureau
`
`(43) International Publication Date
`19 April 2007 (19.04.2007)
`
`(51) International Patent Classification:
`A01N 37/10 (2006.01)
`
`(21) International Application Number:
`PCT/US2006/037078
`
`(22) International Filing Date:
`22 September 2006 (22.09.2006)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`English
`
`English
`
`(30) Priority Data:
`11/241,980
`11/296,216
`11/413,090
`
`4 October 2005 (04.10.2005)
`8 December 2005 (08.12.2005)
`28 April 2006 (28.04.2006)
`
`US
`US
`US
`
`(71) Applicant (for all designated States except US): ACETO
`AGRICULTURAL CHEMICALS CORPORATION
`[US/US]; One Hollow Lane, Lake Success, NY 11042
`(US).
`
`(72) Inventors; and
`(75) Inventors/Applicants (for US only): OLSON, Gary,
`Stephen [US/US]; 1988 Riting Court SE, Salem, OR
`97302 (US). SCHAFER, Ronald, K. [US/US]; 11254 Ca—
`mas, Boise, ID 83709 (US). GILLARD, Grace [GB/GB];
`16 Three Ways, Delarnere Park, Cuddington, Cheshire,
`CW8 2X] (GB).
`
` (10) International Publication Number
`
`WO 2007/044200 A2
`
`(74) Agents: TREANOR, Richard, L. et 31.; OBLON, SP1,
`VAK, MCCLELLAND, MAIER & NEUSTADT, PC,
`1940 Duke Street, Alexandria, VA 22314 (US).
`
`(81) Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN,
`CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, Fl,
`GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP,
`KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT,
`LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MY, MZ,
`NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU,
`SC, SD, SE, SG, SK, SL, SM, SV, SY, Tl, TM, TN, TR,
`TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
`
`(84) Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM,
`ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM),
`European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, Fl,
`FR, GB, GR, HU, IE, IS, IT, LT, LU, LV, MC, NL, PL, PT,
`RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA,
`GN, GQ, GW, ML, MR, NE, SN, TD, TG).
`
`Published:
`
`* without international search report and to be republished
`upon receipt of that report
`
`For two-letter codes and other abbreviations, refer to the ”Guid-
`ance Notes on Codes and Abbreviations ” appearing at the begin-
`ning of each regular issue of the PCT Gazette.
`
`(54) Title: INHIBITION OF TUBER SPROUTING
`
`(57) Abstract: The present invention relates to inhibiting the sprouting of potato tubers using at least one of MCPP, carbetamide,
`pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, and MCPA, salts thereof and esters thereof.
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0001
`Page 0001
`
`
`
`02007/044200A2|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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`

`

`WO 2007/044200
`
`PCT/U82006/037078
`
`. INHIBITION OF TUBER SPROUTING
`
`Reference to Related Applications
`
`This application is claims priority to US. application Serial No. 11/241,980
`
`filed October 4, 2005, to US. application Serial No. 11/296,216 filed December 8,
`
`2005, and to U.S. application Serial No. 11/413,090 filed April 28, 2006 ,all of
`
`which are incorporated herein in their entireties by reference.
`
`Field of the Invention
`
`The present invention relates to the use of at least one of MCPP,
`
`carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP,
`
`MCPA, their salts and esters, and mixtures thereof, to inhibit sprouting of tubers,
`
`particularly potato tubers, and most preferably the sprouting of tubers of stored
`
`potatoes. The application of at least one of MCPP, carbetamide, pronamide,
`
`ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, their salts and
`esters, and mixtures thereof, to tubers also makes up a part ofthe invention, as do
`
`tubers having at least one of MCPP, carbetamide, pronamide, ethofumesate,
`
`mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, their salts and esters, and
`
`mixtures thereof on at least a part of a surface thereof. Salts and esters of these
`
`compounds can also be used in all aspects of the invention. Because potatoes are an
`
`important application of the present invention, they will be discussed in detail below.
`However, the invention is not limited thereto, and includes tubers in general such as
`
`other root crops like sweet potatoes and yams.
`
`Background of the Invention
`
`It is well known in the art to treat tubers such as potatoes with various
`
`chemicals having sprout-inhibiting properties. CIPC (chlorpropham, chlorprophame;
`
`chlor-IPC IUPAC name isopropyl 3-chlorocarbanilate; isopropyl 3-
`
`chlorophenylcarbamate;
`
`Chemical Abstracts name l-methylethyl (3-chlorophenyl)carbamate EEC no. 202-
`
`925-7) has been conventionally used for this purpose for about 40 plus years. More
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0002
`Page 0002
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`WO 2007/044200
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`PCT/U82006/037078
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`recently, chemicals such as various isomers of diisopropylnaphalene and other
`
`substituted naphthalenes have exhibited sprout-inhibiting characteristics.
`
`Potato tubers are often treated with a chemical sprout inhibitor in the storage
`
`season, and may receive another treatment of sprout inhibitor before being packaged
`
`for shipment to retail outlets. In the absence of chemical sprout inhibitors, the
`
`ultimate storage life is greatly reduced by loss of dormancy and early sprouting.
`
`Thus, virtually all potatoes stored mid and long term are treated with chemical
`
`sprout inhibitors.
`
`Potatoes when being dug are frequently bruised, cut and/or abraded. These
`
`injuries to the potatoes oftentimes cause spoilage during shipment, storage and the
`
`like. A process known as suberization occurs naturally which tends to heal many of
`
`these injuries. However, whenever potatoes are stored, which occurs with a
`
`particularly large portion of potatoes harvested in any given year, if healing occurs
`
`slowly, a significant loss of potatoes can occur through spoilage. Early treatment
`
`with certain sprout inhibitors, such as CIPC, may retard the suberization process,
`
`thus contributing to the loss of potatoes through spoilage.
`
`The main sprout inhibitors registered for use on potatoes are (CIPC), maleic
`
`hydrazide (MH), and dimethylnaphthalene (DMN) and Diisopropylnaphthalene
`
`(DIPN). The two chemicals in combination (CIPC plus DIPN) appear to be more
`
`effective at lower concentrations than either of the two chemicals alone.
`
`Simultaneous application of CIPC and DIPN provides improved results over
`
`application of either sprout inhibitors separately.
`
`For example, it is relatively common in the potato storage industry to treat
`
`potatoes with Chloroisopropyl-N—carbamate (CIPC) to prevent or retard
`
`development of sprouts in the potatoes. Even though untreated potatoes are stored at
`
`a cool temperature, for example, generally between about 36— 52 °F, sprouting does
`
`begin to occur after a month or more of storage. Storage of upwards of six to ten
`
`months is typical for stored potatos. Thus, without treatment of a chemical such as
`
`CIPC, the stored potatoes become entangled in sprouts and the whole stored lot of
`
`potatoes may become economically useless. Although early treatment with CIPC
`
`could be advantageous for sprout inhibition purposes, application of CIPC is
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0003
`Page 0003
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`WO 2007/044200
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`PCT/U82006/037078
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`typically delayed until after suberization has occurred inasmuch as CIPC tends to
`
`retard suberization, resulting in accelerated rot and spoilage.
`
`CIPC is typically applied in one or multiple applications to the tubers to be
`
`stored using thermal fogging techniques, sprays and powders. Conventional thermal
`
`fogging involving the application of CIPC into a stream of hot air or onto a hot
`
`surface of 550 -- 1000 °F, to produce a CIPC aerosol. The CIPC aerosol is circulated
`
`through potatoes piled in a potato storage building with the use of fans. Preferably
`
`the potatoes are turgid rather than soft when treated with the CIPC aerosol, since a
`
`pile of softened potatoes may be substantially compressed thereby impeding
`
`distribution of the aerosol. CIPC residue levels, will, however, typically decrease
`
`over time due to biodegration, venting and atmospheric loss. To extend the effective
`
`sprout inhibiting capability of CIPC, further applications may be needed.
`
`CIPC is used in significant quantities world wide and is capable of
`
`suppressing sprouts on stored tubers with the chemical ability to limit cell division.
`
`Increased rates, multiple applications, addition of substituted naphthalene
`
`chemistries coupled with strict storage management strategies have been
`implemented to help reduce sprout development in CIPC treated potatoes. The .
`
`instant invention provides an effective anti-sprouting treatment protocol that does
`
`not use CIPC and/or compliments the use of CIPC.
`
`Summa_ry of the Invention
`
`. The present invention embodies the inventors’ discovery that MCPP,
`
`carbetamide, pronamide (termed “propyzamide” in the UK), ethofumesate,
`
`mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures thereof, including
`
`the use of salts and esters thereof, inhibit the sprouting of tubers, particularly potato
`
`tubers, and that they can be used, if desired, in the same manner as conventional
`
`sprout inhibitors registered for use on potatoes. Of course, in addition to being used
`
`alone, MCPP, carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4
`
`DB, 2,4 DP, MCPA, and mixtures thereof (including the use of salts and esters
`
`thereof) can be used in concert with any other sprout inhibitor(s). While certain of
`
`MCPP, carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB,
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0004
`Page 0004
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`WO 2007/044200
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`PCT/U82006/037078
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`2,4 DP, MCPA, and mixtures thereof have been known for other uses, the inventors’
`
`discovery that MCPP, carbetamide, pronamide, ethofumesate, mefluidide,
`
`paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures thereof, as well as salts and
`
`esters thereof, inhibit the sprouting of tubers represents a new use for these
`
`materials.
`
`Detailed Description of the Preferred Embodiments
`
`The active agents whose use in inhibiting the sprouting of tubers forms the
`
`basis of the present invention are known as MCPP, carbetamide, pronamide,
`
`ethofilmesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA. As explained
`
`further below, salts and esters thereof may also be used herein.
`
`MCPP:
`
`Other names for MCPP include Mecoprop, mechlorprop, mécoprop,
`
`Mecoprop-P, Kilprop, Mecopar, Triester-II, Mecomin-D, Mecopex, Mecomec, and
`
`U46 KV Fluid (41, 43), the technical brochures, data sheets, and MSDS sheets
`
`thereof all incorporated herein by reference. Preferred MCPP compounds useful
`
`herein include (RS)-2-(4—chloro-o-tolyloxy)propionic acid (i)-2-(4—chloro-2—
`
`methylphenoxy)propanoic acid, CAS RN [7085-19—0] racemate; [93-65—2]
`
`(formerly used for mecoprop) unstated stereochemistry Development Codes RD
`
`4593 (Boots); L143 (Marks), 2-(4—Chloro-o—tolyloxy) propionic acid otherwise
`
`known as 2—(4-Chloro-2-methylpheno;(y)propanoic acid. Compounds with CAS #5
`
`93-65—2 and 7085—19-0 are also preferred, as are (RS)—2—(4-chloro-0-
`
`tolyloxy)propionic acid, (R)-2-(4-Chloro-2-methylphenoxy)propionic acid and (S)-
`
`2-(4—Chloro-2—methylphenoxy)propionic acid. Also preferred are mecoprop-
`
`dimethylammonium [32351—70-5], mecoprop-diolamine [1432—14-0], mecoprop-
`ethadyl, mecoprop—isoctyl [28473-03-2], mecoprop-potassium [1929-86-8],
`
`mecoprop—sodium [19095-88-6], mecoprop—trolamine [53404-61-8]. A preferred
`
`MCPP compound for use in the present invention has the formula:
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0005
`Page 0005
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`WO 2007/044200
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`PCT/U82006/037078
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`Cl
`
`CH3
`CI
`A?
`l
`OMCH—C
`‘\
`OH
`
`CH3,
`
`Included are racemic mixtures and all stereoisomers (molecules that are identical in
`
`atomic constitution and bonding, but differ in the three-dimensional arrangement of
`
`the atoms) thereof, including individual enantiomers and mixtures thereof
`
`Similarly, all salts and esters of the above formula (including racemates and
`
`enantiomers thereof) and of all MCPP compounds are useful herein, especially the
`
`potassium, sodium and lithium salts thereof and the C1.-C24 esters thereof. As is
`
`known by those of skill in this art, the salts and esters of the above formula replace
`
`the hydrogen (H) of the hydroxyl group (—OH) with, e. g., a metal ion (e.g., Na+, K+,
`
`etc.) or, e.g., an alkyl group (e.g., -CI-I3), respectively. Preferred MCPP salts include
`
`the sodium and potassium salts. Preferred esters include C1-C24 branched or
`
`unbranched, substituted or unsubstituted alkyl and alkenyl esters, preferably C1-C10
`
`unbranched, Substituted or unsubstituted alkyl esters. "Substituted" refers to the
`
`replacement of hydrogen with a monovalent or divalent radical. Suitable
`
`substitution groups include, for example, hydroxyl, nitro, amino, imino, cyano, halo,
`
`thio, thioamido, amidino, imidino, 0X0, oxamidino, methoxamidino, imidino,
`
`guanidino, sulfonamido, carboxyl, formyl, loweralkyl, haloloweralkyl, loweralkoxy,
`
`haloloweralkoxy, loweralkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl,
`
`heteroarylcarbonyl, heteroaralkylcarbonyl, alkylthio, aminoalkyl, cyanoalkyl, and
`
`the like.
`
`As used herein, the terms “MCPP” and “MCPP compound” include all of these
`
`materials including all acids, salts and esters thereof, particularly C1-C24 esters
`
`thereof. In Europe MCPP is sometimes referred to as “CMPP.” As used herein
`
`“MCPP” and “MCPP compound” include CMPP.
`
`Carbetamide:
`
`Carbetamide has the following structure:
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0006
`Page 0006
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`WO 2007/044200
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`PCT/USZOOG/037078
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`and is variously known as (R)—1—(ethylcarbamoyl)ethyl carbanilate and (2R)—N—
`
`ethyl-Z—[[(phenylamino)carbonyl]oxy]propanamide. It has CAS No. 16118—49-3 and
`
`the empirical formula C12H16N203.
`
`Pronamide:
`
`Pronamide has the following structure:
`
`c1
`
`\‘ /
`
`m
`
`3H _
`3
`E
`
`got
`C
`x
`“swag—cam
`
`H
`
`CH3
`
`and is variously known as propyzamide, ,5—dichloro—N—(1,1—
`
`dimethylpropynyl)benzamide and 3,5-dichloro—N—(1 ,1 -dimethyl—2—
`
`propynyl)benzamide. It has CAS No. 23950—58—5 and the empirical formula
`
`C12H11C12N.
`
`Ethofumesate:
`
`Ethofumesate has the structure:
`
`G
`ll
`3143—3—13“
`ll
`0
`
`«('0
`
`CH1
`
`CHEW CH3
`/‘
`0
`CH3
`
`6
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0007
`Page 0007
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`WO 2007/044200
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`PCT/U82006/037078
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`and is variously known as (RS)—2—ethoxy-2,3—dihydro—3,3-dirnethylbenzofi1ran-S—y1
`
`methanesulfonate and 2-ethoxy—2,3—dihydro—3,3—dimethyl-5—benzofuranyl
`
`methanesulfonate. It has Registration No. 26225-79—6 and an empirical formula
`
`C13H18058.
`
`Mefluidide:
`
`Mefluidide has the structure:
`
`
`
`and is variously known as 5’—(l,1,1~trifluoromethanesulfonamido)acet—2’,4’-xy1idide
`
`and N— [2,4-dimethyl-5—[[(trifluoromethyl)sulfonyl]amino]phenyl]acetamide. It has
`
`CAS No. 53780—34—0 and empirical formula C11H13F3N203S.
`
`Paclobutrazol:
`
`Paclobutrazol has the structure:
`
`CH3
`
`KNR
`
`a
`
`I
`
`H C—E—CR
`
`:2
`
`Nfi-fiHmflH—DH
`NW
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0008
`Page 0008
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`(3H2
`
`\ C
`
`l
`
`

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`WO 2007/044200
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`PCT/U82006/037078
`
`and is variously known as (ZRS, 3RS)-l-(4-chlorophenyl)—4,4-dimethyl-2-(1H-l,2,4-
`
`triazol— l -y1)pentan-3—ol and el—(dR,[3R)-[3-[(4-chlorophenyl)methyl] -0L—(1 , 1 -
`
`dimethylethyl)-1H-1,2,4-triazole—1-ethanol. It has Registration No. 7673 8-62-0 and
`
`the empirical formula C15H20C1N30.
`
`2,4 DB:
`
`2,4 DB has the structure:
`
`Cl
`
`(:1
`
`C}
`it
`
`0H
`
`It is variously known as 4—(2,4—dichlorophenoxy)butyric acid and 4-(2,4-
`
`dichlorophenoxy)butanoic acid. It has CAS No. 94—82—6 and the empirical formula
`
`C10H1001203, This material can be used as a salt, or an ester, such as 2,4-DB-butyl,
`
`2,4-DB-dimethylammonium [275 8—42—1], 2,4-DB-isoctyl, 2,4-DB-potassium
`
`[19480-40—1], 2,4—DB-sodium [10433—59—7], etc.
`
`2,4 DP:
`
`2,4 DP has the structure:
`
`Cl
`
`.
`
`c1
`
`CH3
`l
`
`CI-eCH-Ci
`
`0
`
`I
`
`DH
`
`It is variously known as (RS)-2-(2,4—dichlorophenoxy)propionic acid and 2-(2,4—
`dichlorophenoxy)propanoic acid. It has CAS No. 120-36-5 and the empirical
`formula CgHgCIZO3, This material can be used as a salt, or an ester, such as ’
`
`dichlorprop—butotyl, dichlorprop—dimethylammonium, dichlorprop—ethylammonium,
`
`dichlorprop—isoctyl [28631—35-8], dichlorprop-potassium. The (R)—isomer of this
`
`substance has the common name dichlorprop—P.
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0009
`Page 0009
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`MCPA:
`
`MCPA has the general structure:
`
`Cl
`
`It is variously known as (4—chloro—2-methylphenoxy)acetic acid and 4—chloro—o-
`
`tolyloxyacetic acid. It has CAS No. 94—74—6 and the empirical formula C9H9C103,
`
`The name “metaxon” was used in the former USSR. This material can be used as a
`
`salt, or an ester, such as for example MCPA—butotyl [19480—43—4], MCPA—butyl
`
`[1713 —12—8], MCPA-dimethylammonium [2039—46—5] , MCPA—diolamine [20405 -
`
`19-0], MCPA-2—ethylhexyl [29450—45— 1], MCPA—isobutyl [1713-1 1-7], MCPA-
`
`isoctyl [26544-20-7], MCPA-isopropyl [2698—40—0], MCPA-methyl [2436—73—9],
`MCPA—olamine [6365-62-4], MCPA—potassium [52217l6-9], MCPA—sodium [3653-
`
`48-3], MCPA—trolamine [4245 9-68-7].
`
`Included as useful herein for all of MCPP, carbetamide, pronamide,
`
`ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures
`
`thereof, are racemic mixtures and all stereoisomers (molecules that are identical in
`
`atomic constitution and bonding, but differ in the three—dimensional arrangement of
`
`the atoms) thereof, including individual enantiomers and mixtures thereof.
`
`Similarly, all salts and esters of the above formulae (including racemates and
`
`enantiomers thereof) are useful herein, especially the potassium, sodium and lithium
`
`salts thereof and the C1-C24 esters thereof. As is known by those of skill in this art,
`
`the salts and esters of the above formula replace, e. g.,
`
`the hydrogen (H) of the
`
`hydroxyl group (—OH) with, e.g., a metal ion (e. g., Na+, K+, etc.) or a
`
`dimethylamine group, etc., or a carbonylhydrocarbon group (COR) or, for MCPP,
`
`2,4 DB 2,4-DP and MCPA, e.g., a hydrocarbon group such as an alkyl group (e.g., ~
`
`CH3), respectively. Alternatively, or in addition, salts may be formed at the nitrogen
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0010
`Page 0010
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`WO 2007/044200
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`PCT/U82006/037078
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`atom by addition, of, e. g., acids, etc. Those of skill in this art are aware of where
`
`and how salts and esters of the noted compounds herein can be made and used in
`
`View of this disclosure. Preferred salts include the sodium and potassium salts as
`
`well as the hydrohalide salts such as hydrochloride, etc. Preferred esters include Cl-
`
`C24 branched or unbranched, substituted or unsubstituted alkyl and alkenyl esters,
`
`preferably 01—010 unbranched, substituted or unsubstituted alkyl esters.
`
`"Substituted" refers to the replacement of hydrogen with a monovalent or divalent
`
`radical. Suitable substitution groups include, for example, hydroxyl, nitro, amino,
`
`imino, cyano, halo, thio, thioamido, amidino, imidino, oxo, oxamidino,
`
`methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, loweralkyl,
`
`haloloweralkyl, loweralkoxy, haloloweralkoxy, loweralkoxyalkyl, alkylcarbonyl,
`arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, alkylthio,
`
`aminoalkyl, cyanoalkyl, and the like.
`
`As used herein, the term “tuber” is inclusive of "potato tuber." "Potato tuber“
`
`refers to the underground storage organ of the potato plant (Solanum tuberosum).
`
`The potato tuber is a modified stem and includes buds that can sprout and form new
`
`potato plants. The term “(potato) tubers” refers to both tubers generally and to
`
`potato tubers. Preferred potatoes include Russet Burbank, Ranger Russet, Umatilla
`
`Russet, Shepody, Norkotah Russet, Yukon Gold, Norchip, Gem Russet, Atlantic,
`
`Chipeta, Snowden, and Dark Red Norland
`
`The phrase "effective to inhibit sprouting" means that: (a) the number,
`
`and/or the weight, of stems (sprouts) growing from a defined number of (potato)
`
`tubers contacted with at least one of MCPP, carbetamide, pronamide, ethofumesate,
`
`mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures thereof, salts and
`
`esters thereof, in accordance with the present invention is less than the number,
`
`and/or the weight, of stems growing from the same number of control (potato)
`
`tubers (of the same cultivar as the treated (potato) tubers) that were not contacted
`
`with a sprouting inhibitor; and/or (b) the average rate of growth of stems growing
`
`from a defined number of (potato) tubers contacted with at least one of MCPP,
`
`carbetamide, pronamide, ethofumesate, mefluidide, pac‘lobutrazol, 2,4 DB, 2,4 DP,
`
`MCPA, and mixtures thereof, salts and esters thereof, in accordance with the present
`
`invention is less than the average rate of growth of stems growing from the same
`
`10
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0011
`Page 0011
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`PCT/U82006/037078
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`number of control (potato) tubers (of the same cultivar as the treated (potato) tubers)
`
`that were not contacted with a sprouting inhibitor. Such inhibition can be at any
`
`time as compared to the control. As understood by those in this field, the concept of
`
`inhibition is meaningful when control tubers show activity being inhibited in tubers
`
`contacted with at least one of MCPP, carbetamide, pronamide, ethofumesate,
`mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures thereof, salts and
`
`esters thereof. Another preferred measure of inhibition is a comparison between the
`
`total amount of “dormant + sprout up to 3 mm” tubers at, e.g., 50 days after harvest
`
`as compared to untreated control. Whichever measure is used, preferred amounts of
`
`inhibition include less than 1%, 1%, 3%, greater than 3%, 5%, 8%, 10%, 20%,
`
`30%,etc. to 100%.
`
`As used herein the phrase “at least one of MCPP, carbetamide, pronamide,
`
`ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures
`
`thereof” includes salts and esters thereof, and any mention of an invention
`
`compound or material (e.g., carbetamide) herein includes its salts, and includes its
`
`salts and esters for any invention compound capable of forming a salt ans/or an ester
`
`such as MCPP, paclobutrazol, 2,4 DB, 2,4 DP, and MCPA.
`
`The MCPP, carbetamide, pronamide, ethofumesate, mefluidide,
`
`paclobutrazol, 2,4 DB, 2,4 DP, and MCPA materials, salts and esters thereof, used
`
`herein can be purchased commercially, or synthesized by one of ordinary skill in the
`
`art. They can be used alone or in mixture, and can be applied together with other
`
`materials such as other sprout inhibitors. By “together,” we mean that the MCPP,
`
`carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP,
`
`MCPA, and mixtures thereof can be used in mixture with other materials such as
`
`active agents upon application to, e. g., potatoes, and/or can be used sequentially
`
`before, during, and/or after application of any other material. Useful combinations
`
`of MCPP, carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4
`
`DB, 2,4 DP, MCPA, and mixtures thereof with other materials include combinations
`
`with one or more of MCPP, MCPA, CIPC, 2,4-D and dicamba. However,
`
`formulations including dicamba are not preferred due to the long residual of
`
`dicamba and the harmful effects that minute residues of dicamba cause in potato.
`
`Potatoes treated with dicamba or the surfaces contacted by these potatoes can render
`
`11
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0012
`Page 0012
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`WO 2007/044200
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`PCT/U82006/037078
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`the storage and handling equipment trucks and such unfit for handing seed potatoes.
`
`In addition, and regardless whether MCPP, carbetamide, pronamide, ethofumesate,
`
`mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures thereof are utilized
`
`with any other active agent, the present invention includes multiple applications of
`
`MCPP, carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB,
`
`2,4 DP, MCPA, and mixtures thereof on the same tuber, generally where the
`
`applications are spaced over certain time intervals.
`
`In general, the present invention includes any application of MCPP,
`
`carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP,
`
`MCPA, and mixtures thereof to tubers, and particularly includes application to
`
`potato plants in the field before the potatoes are harvested, and/or application after
`
`the potatoes are harvested but before they are stored, and/or application after the
`
`potatoes are in storage. In a preferred embodiment the MCPP, carbetamide,
`pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and
`
`mixtures thereof is applied Via an aerosol, spray or thermal fog, as a dust, or in
`
`microencapsulated form to harvested potatoes. Methods of application also include
`
`via aerosol can and via smoke generators, for example for treatment in rail cars.
`
`MCPP, carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB,
`
`2,4 DP, MCPA, and mixtures thereof may also be first or subsequently applied after
`
`tubers (potatoes) have been harvested and stored for a sufficient period that bruises
`
`and cuts have healed, i.e., suberization has occurred. In another aspect of the
`
`invention, the MCPP, carbetamide, pronamide, ethofumesate, mefluidide,
`
`paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures thereof is applied such that it
`
`inhibits sprouting during the potato shipping and distribution process.
`
`In accordance with the foregoing, the present invention provides methods for
`
`inhibiting sprouting of potato tubers, the methods each including the step of
`
`contacting a potato tuber with an amount of at least one of MCPP, carbetamide,
`
`pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and
`
`mixtures thereof, wherein the amount of the at least one carbetamide, pronamide,
`ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA is effective to
`
`inhibit potato tuber sprouting. Typically, the at least one MCPP, carbetamide,
`
`pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, is
`
`12
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0013
`Page 0013
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`WO 2007/044200
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`PCT/U82006/037078
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`applied simultaneously, or substantially simultaneously, to numerous, harvested,
`
`potato tubers. In the practice of the methods of the invention the at least one of
`
`MCPP, carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB,
`
`2,4 DP, MCPA is applied after the potato tubers have been harvested, but typically
`
`not later than the onset of sprouting. In some embodiments of the methods of the
`
`invention, the effective amount of at least one MCPP, carbetamide, pronamide,
`
`ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA is that amount
`
`sufficient to provide a dosage of from far less than 1 mg per/ 1 kg (parts per million)
`
`potato tubers to, e. g., 100 ppm, 500 ppm, and above. Preferred amounts include 0.01,
`
`0.05, 0.1, 0.2, 0.3, 0.5, 1, 2, 3, 5, 8, 10, 15, 20, 25, 30, 35, 40, 50, 60, etc. ppm.
`
`The instant invention includes a method of inhibiting the sprouting of stored
`
`tubers, especially potatoes, by applying a first sprout inhibiting chemical to the
`
`stored potatoes and then applying a second sprout inhibiting chemical at a later time,
`
`where at least one of the sprout inhibiting chemicals is at least one of MCPP,
`carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP,
`
`MCPA. Because multiple applications of MCPP, carbetamide, pronamide,
`
`ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures
`
`thereof makes up a part of the invention, the “second sprout inhibiting chemical”
`
`can be any of MCPP, carbetamide, pronamide, ethofumesate, mefluidide,
`paclobutrazol, 2,4 DB, 2,4 DP, MCPA, and mixtures thereof. Other useful sprout
`inhibitors include CIPC, MCPP, and DMN (dimethyl naphthalene) or DIPN,
`
`especially 2,6 Disopropyl naphthalene. Multiple materials may be applied together,
`
`or the time elapsed between application of the first and second chemical
`
`applications may be from a few moments to several months. The second chemical is
`
`generally applied at a time span when the efficacy of the sprout inhibiting
`
`characteristics of the first chemical is waning. Application may be in any fashion,
`
`and may be according to the methods detailed in any of U.S.
`
`4226179, 6432882, 6790469, 6855669, 6310004, 6107247, 6010728, 6001773,
`
`5965489, 5436226, 5,622,912 , 5,811,372, and 6855669 all incorporated herein by
`
`reference.
`
`In accordance with the foregoing, in one aspect, the present invention
`
`provides methods for treating (potato) tubers, the methods each comprising the step
`
`13
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0014
`Page 0014
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`

`

`WO 2007/044200
`
`PCT/U82006/037078
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`of contacting a (potato) tuber with an amount of at least one of MCPP, carbetamide,
`
`pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP and MCPA.
`
`Preferably the amount of the at least one of MCPP, carbetamide, pronamide,
`
`ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP and MCPA is an amount
`
`effective to inhibit (potato) tuber sprouting. However, this is not required. For
`
`example, when the at least one of MCPP, carbetamide, pronamide, ethofumesate,
`
`mefluidide, paclobutrazol, 2,4 DB, 2,4 DP and MCPA is used together with another
`
`sprout inhibitor, the at least one MCPP, carbetamide, pronamide, ethofumesate,
`
`mefluidide, paclobutrazol, 2,4 DB, 2,4 DP and MCPA can be used in an amount less
`
`than that effective to inhibit potato tuber sprouting. Preferably, of course, the total
`
`amount of sprout inhibitor (i.e., the amount of the at least one of MCPP,
`
`carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP,
`
`and MCPA compound, mixture thereof, and any additional sprout inhibitor(s)) is
`
`effective to inhibit potato tuber sprouting. Such additional sprout inhibitors include,
`
`e. g. CIPC, MCPP, chlorpropham, maleic hydrazide, diisopropylnaphthalene,
`
`dimethylnaphthalene, carvone, aliphatic aldehydes and ketones, eugenol,
`
`benzothiazide, ethylene, aromatic acids (e.g., anisic acid, coumaric acid, gallic acid),
`
`rape oil methyl ester, medium and long-chain alcohols, jasmonates, aromatic
`
`aldehydes (e.g., benzaldehyde, salicaldehyde, cinnamaldehyde,
`
`hydrocinnamaldehyde, cuminaldehyde, thymol), monoterpenes (e.g., cineole,
`
`fenchone, menthol), and essential oils (e.g., mint oils)). In addition, sprout inhibitors
`
`listed in the following US patents, all incorporated herein by reference, may be used:
`
`6,958,167
`
`6,946,155
`
`6,855,669
`
`6,790,469
`
`6,541,054
`
`6,495,710
`
`6,432,882
`
`6,403,536
`
`6,375,999
`
`6,338,296
`
`6,322,002
`
`6,310,004
`
`6,107,247
`
`6,068,888
`
`14
`
`1,4 GROUP, INC.
`1,4 GROUP, INC.
`Exhibit 1005
`Exhibit 1005
`Page 0015
`Page 0015
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`

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`WO 2007/044200
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`PCT/U82006/037078
`
`6,010,728
`
`6,001,773
`
`5,965,489
`
`5,935,660
`
`5,918,537
`
`5,849,664
`
`5,580,596
`
`5,436,226
`
`5,009,152
`
`4,977,825
`
`4,887,525
`
`4,226,179
`
`Where a combination of sprout inhibitors is applied in a single composition it is
`
`preferred that the composition comprise A) at least one of MCPP, carbetamide,
`
`pronamide, ethofumesate, mefluidide, paclobutrazol, 2,4 DB, 2,4 DP and MCPA
`
`and, further, B) at least one other sprout inhibitor, such as CIPC. The weight ratio of
`
`A/B can vary Without limitation, and is preferably 99/1, 95/5, 90/10, 85/15, 80/20,
`
`75/25, 70/30, 65/35, 60/40, 55/45, 50/50, 45/55, 40/60, 35/65, 30/70, 25/75, 20/80,
`
`15/85, 10/90, 5/95, 1/99, etc., including all values and subranges between less than
`
`100 and greater than 0. Preferably, the amount of sprout inhibitor applied, in ppm,
`
`has these same values and, for example, include A/B ratios such as 121.1, 1:4.4, ,
`
`1:11, etc. A preferred example is the application of, e.g., 10 ppm MCPP + 11 ppm
`
`CIPC, 1 ppm MCPP + 11 ppm CIPC, etc. Where multiple sprout inhibitors are
`
`applied, Whether simultaneously from the same or different compositions or applied
`
`in a time separated manner, useful amounts of the inhibitor(s) according the
`
`invention (MCPP, carbetamide, pronamide, ethofumesate, mefluidide, paclobutrazol,
`
`2,4 DB, 2,4 DP, MCPA, and mixtures thereof) and of another inhibitor or inhibitors
`
`(Inhibitor X) include less than 1, 1, 3, 5, 8, 10, 15, 18, 20, 30, 40, 50, 70, 90, 100,
`
`120, 150, 1