PaperNo. __
`
`Filed on behalf of: Junior Party Levin
`
`By: Gary J. Gershik
`Registration No. 39,992
`Cooper & Dunham LLP
`30 Rockefeller Plaza, 20th Floor
`New York, New York 10112
`Tel: (212) 278-0400
`Fax: (212) 391-0525
`E-mail: ggershik@cooperdunham.com
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`ANATLEVIN
`and MICHAEL GRABARNICK,
`Junior Party,
`(Application 13/926,389)
`
`V.
`
`ANDREA PASTORIO
`and PAOLO BETTI
`Senior Party,
`(Patent 8,304,559)
`
`Patent Interference No. 105,995 (SGL)
`(Technology Center 1600)
`
`SIXTH DECLARATION OF GORDON W. GRIBBLE,
`
`FINCHIMICA EXHIBIT 2028
`ADAMA MAKHTESHIM v. FINCHIMICA
`CASE IPR2016-00577
`
`
`
`Filed on behalf of: Junior Party Levin
`
`By: Gary J. Gershik
`Registration No. 39,992
`Cooper & Dunham LLP
`30 Rockefeller Plaza, 20th Floor
`New York, New York 10112
`Tel: (212) 278-0400
`Fax: (212) 391-0525
`E-mail: ggershik@cooperdunham.com
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`ANATLEVIN
`and MICHAEL GRABARNICK,
`Junior Party,
`(Application 13/926,389)
`
`V.
`
`ANDREA PASTORIO
`and PAOLO BETTI
`Senior Party,
`(Patent 8,304,559)
`
`Patent Interference No. 105,995 (SGL)
`(Technology Center 1600)
`
`SIXTH DECLARATION OF GORDON W. GRIBBLE,
`
`FINCHIMICA EXHIBIT 2028
`ADAMA MAKHTESHIM v. FINCHIMICA
`CASE IPR2016-00577
`
`
`
`PaperNo. __
`
`Filed on behalf of: Junior Party Levin
`
`By: Gary J. Gershik
`Registration No. 39,992
`Cooper & Dunham LLP
`30 Rockefeller Plaza, 20th Floor
`New York, New York 10112
`Tel: (212) 278-0400
`Fax: (212) 391-0525
`E-mail: ggershik@cooperdunham.com
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`,I
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`ANATLEVIN
`and MICHAEL GRABARNICK,
`Junior Party,
`(Application 13/926,389)
`
`V.
`
`ANDREA PASTORIO
`and PAOLO BETTI
`Senior Party,
`(Patent 8,304,559)
`
`Patent Interference No. 105,995 (SGL)
`(Technology Center 1600)
`
`SIXTH DECLARATION OF GORDON W. GRIBBLE, PH.D.
`
`LEVIN EXHIBIT 1044
`Pastorio v. Levin
`Interference No. 105,995
`
`
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`Interference No. 105,995
`
`1. My background, qualifications, and other information are set forth in my
`
`previous declarations submitted in this proceeding. Exs. 1001, 1013, 1018,
`
`1022.
`
`2. Details about my professional experience are described in my curriculum
`
`vitae, submitted herewith as Ex. 1002.
`
`3. I am aware that a patent interference (Interference No. 105,995) has been
`
`declared between Junior Party Anat Levin and Michael Grabamick
`
`("Levin"), U.S. Patent Application Serial No. 13/926,389 (Ex. 2002), and
`
`Senior Party Andrea Pastorio and Paolo Betti ("Pastorio"), U.S. Patent No.
`
`8.304,559 {"the '559 patent") (Ex. 2001).
`
`4. I have been retained by Cooper & Dunham LLP, the law firm representing
`
`Levin in the patent interference, and am being compensated at my standard
`
`hourly rate of $400 per hour and $600 per hour for deposition testimony.
`
`5. I have been informed that the real party in interest for Junior Party Levin is
`
`Adama Makhteshim Ltd., and that the real party in interest for Senior Party
`
`Pastorio is Finchimica, S.p.A. I do not have any financial interest in either
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`Adama Makhteshim Ltd. or Finchimica, S.p.A., and I do not have any
`
`financial interest in the outcome of this patent interference.
`
`6. I have had no contact with the Levin inventors or the Pastorio inventors.
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`2
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`
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`Interference No. 105,995
`
`7. My opinions provided in this declaration are as an independent technical
`
`expert.
`
`8. I have been informed that the '559 patent issued on November 6, 2012 from
`
`U.S. Serial No. 13/498,245, which was a national stage entry of PCT
`
`International Application No. PCT/IB201 l/052304, filed May 6, 2011, and
`
`published as PCT
`
`International Application Publication No. WO
`
`2012/004692 on January 12, 2012 ("the Pastorio PCT"), which claims
`
`priority to Italian Patent Application No. BS2010A0118, filed July 7, 2010
`
`("the Pastorio priority application"). Exs. 2010, 2011, 2017.
`
`9. I understand that Junior Party Levin is preparmg a motion m this
`
`interference for judgment on the basis that the claims of the '559 patent are
`
`invalid over the prior disclosure of WO 2007/122440 Al ("WO '440"). Exs.
`
`2001, 2009.
`
`10 .I have been asked to provide my opinions on what would have been the
`
`knowledge and understanding of a person having ordinary skill in the art
`
`("POSA") as of the July 7, 2010, claimed priority date of the Pastorio
`
`priority application, including the meaning of certain claim terms and
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`limitations and the scope of the claims of the '559 patent.
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`Interference No. 105,995
`
`11.A person having ordinary skill in the art as of July 7, 2010 would have had
`
`(1) a bachelor's or master's degree in chemistry or a related discipline and
`
`have at least five years of experience in synthetic organic chemistry,
`
`including sulfide oxidation or (2) a Ph.D. degree or equivalent in organic
`
`chemistry and two years of experience in synthetic organic chemistry,
`
`including sulfide oxidation.
`
`12. The knowledge of a person having ordinary skill in the art as of the May 6,
`
`2011 filing date of the Pastorio PCT application would have been
`
`substantially the same as on the July 7, 2010 filing date of the Pastorio
`
`priority application. Accordingly, the understanding of a person having
`
`ordinary skill in the art as of July 7, 2010 would have been the same as the
`
`understanding of a person having ordinary skill in the art as of May 6, 2011.
`
`In fact the understanding of a person having ordinary skill in the art would
`
`have been the same throughout the year 2010.
`
`13 .In forming my opinions, I have reviewed and understood the '5 5 9 patent in
`
`its entirety and the prosecution history of the '559 patent.
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`
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`Interference No. 105,995
`
`14. The claims of the '559 patent relate to a sulfide oxidation step in the
`
`preparation of fipronil and closely related compounds. Ex. 2001, cols. 9-10.
`
`Upon oxidation the sulfide group becomes a sulfoxide group; with the
`
`sulfoxide group, the compound is fipronil. The oxidation reaction turning
`
`sulfides to sulfoxides is a general and widely known reaction.
`
`15 .I have also read and understood English
`
`language
`
`translations of
`
`BS2010A01 l8 and WO 2012/004692, from which the '559 patent claims
`
`priority. Exs. 2011, 2012. There are a number of differences between the
`
`disclosures of BS2010A0118 and
`
`the
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`'559 patent.
`
`For example,
`
`BS2010A0118 describes only a process that uses dichloroperacetic acid to
`
`oxidize compound of formula (II) without the use of solvents or strong acids.
`
`There is no disclosure in BS201 OAO 118 that oxidation of compound of
`
`formula (II) can proceed merely in the presence of but without involvement
`
`of dichloroacetic acid.
`
`16.Claim 1 of the '559 patent in relevant part is a method for the preparation of
`
`the compound having the following general formula (I):
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`I
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`Interference No. 105,995
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`(I)
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`wherein R 1 and R2 are independently hydrogen or halogen; through
`
`oxidation of a compound having the general formula (II) in the presence of
`
`dichloroacetic acid and of an oxidizing agent:
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`(II)
`
`wherein R 1 and R2 are defined as above, where the oxidizing agent is
`
`selected from the group comprising benzoyl peroxides, sodium peroxides, t-
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`1 O
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`butyl peroxides and/or hydrogen peroxide, and wherein the oxidation is
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`6
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`
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`conducted in the absence of trichloroacetic and/or trichloroperacetic acid.
`
`Interference No. 105,995
`
`Ex. 2001, claim 1 ( emphasis added).
`
`The Claim Terms
`
`17.I have been informed that the terms of a patent claim in this interference
`
`should be given their broadest reasonable interpretation.
`
`18.Although some of the terms of claim 1 and claims dependent thereon are
`
`uncertain, a POSA would understand at least the following:
`
`19.Formula I covers fipronil and Formula II covers 5-amino-1-(2,6-dichloro-4-
`
`trifluoromethylpheny 1 )-3-cyano-4-trifluoromethy lthio
`
`pyrazole
`
`("Compound 420").
`
`20.The oxidizing agent in each of claims 1-12 can be hydrogen peroxide.
`
`21. The claimed sulfide oxidation step takes place in the presence of
`
`dichloroacetic acid ("DCA") and the oxidizing agent, but then dichloracetic
`
`acid need not form dichloroperacetic acid (except in claims 4 and 5) or take
`
`part in the oxidation reaction.
`
`22. The language "oxidation ... in the presence of dichloroacetic acid" means
`
`that oxidation of the sulfide takes place with at least some amount of DCA
`
`present in the reaction mixture but does not require that DCA be present in
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`7
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`Interference No. 105,995
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`any specified amount or that it have any specified function or role. Dr.
`
`Trost has acknowledged that "Nothing in claim 1 ... requires that ... the
`
`dichloroacetic acid recited in claim 1 . . . be oxidized to dichloroperacetic
`
`acid through the oxidizing agent. Ex. 2018 at~ 23.
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`23.For example, each of claims 1-12 encompass a sulfide oxidation driven by
`
`a peroxide and sulfuric acid. To the extent that any amount of DCA is also
`
`present, the claim language would be satisfied.
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`24.Claim 1 is not at all limited in terms of, e.g., proportion of components,
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`time, reaction rate, yield, selectivity, temperature, commercial suitability or
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`scale. Accordingly, for example, any reaction process that produces some
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`fipronil by oxidizing 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)-3-
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`cyano-4-trifluoromethylthio pyrazole in the presence of an oxidizing agent
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`and DCA, and in the absence of trichloroacetic acid (TCA) and/or
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`trichloroperacetic acid (TCP A) would fall within the scope of claim 1.
`
`25.The POSA would understand each of claims 1-12 to encompass a process
`
`in which any amount or yield of fipronil is produced and with any reaction
`
`by-products.
`
`26.Claims 1-12 do not recite or require a strong acid such as sulfuric acid.
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`Interference No. 105,995
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`2 7.I consider the breadth of claims 1-12 as significant because sulfide
`
`oxidations are standard well-known reactions.
`
`Sulfide Oxidations are Simple, Robust, Well-Known Reactions
`
`28.0xidation of a sulfur in organic compounds is a common application for
`
`organic peracids, and a POSA would have understood that stronger parent
`
`acids result in more highly reactive peracids when treated with a peroxide.
`
`Ex. 1009 at § 7.2.1.1; Exs. 1014, 1015, 1024. These cited references are
`
`representative of the knowledge of POSA at the time.
`
`29. The POSA would have been aware that hydrogen peroxide (H20 2) is a
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`simple oxidant albeit less reactive as an oxidant than most other peracids.
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`30.The POSA would have been aware that peracetic acid is a common oxidant,
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`and that stronger more acidic halogenated acetic peracids are available, for
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`example dichloracetic acid (DCA) trichloroacetic acid (TCA)and
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`trifluoracetic acid (TFA).
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`31.Furthermore, the use of stronger acids such as sulfuric acid in sulfide
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`oxidations were known to the POSA, including in conjunction with the use
`
`of hydrogen peroxide. Ex. 1016. This reference is representative of the
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`knowledge a POSA possessed at the time.
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`32.A POSA would have known that TF A, TCA and DCA are all halogenated
`
`Interference No. 105,995
`
`derivatives of acetic acid, each differing from acetic acid by containing one
`
`or more halogen atoms in place of corresponding hydrogen atoms in acetic
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`acid. The replacement of one or more hydrogen atoms in acetic acid with a
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`halogen, e.g. chlorine of fluorine, results in an acid that is more acidic than
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`acetic acid. A property of acetic acid and of each of TF A, TCA and DCA
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`is that each can form a corresponding peracid when mixed with hydrogen
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`peroxide. Thus, in the presence of hydrogen peroxide, TF A forms
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`trifluoroperacetic acid (TFP A), TCA forms trichloroperacetic acid (TCP A),
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`and DCA forms dichloroperacetic acid (DCPA). A POSA was aware that
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`the oxidation of the sulfide precursor into fipronil can proceed through
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`oxidation by the peracid. The '559 patent acknowledges this in column 1,
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`line 66 to column 2, line 3, lines 21-27.
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`33.The acidity of an organic acid, which is important to its reactivity in
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`oxidation, can be expressed in terms of a pKa value.
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`34. The following table shows the relative acidities of halogenated derivatives
`
`of acetic acid, where Ka is the dissociation constant of the acid, and where
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`lower pKa and higher Ka means a stronger acid:
`
`Ka as normalized to acetic acid
`PKa Ka
`Name
`4.76
`0.0000174 1.0
`Acetic Acid
`Chloroacetic acid 2.86
`0.00138
`79
`(CA)
`
`10
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`
`
`Interference No. 105,995
`
`'
`
`Dichloroacetic
`acid (DCA)
`I Trichloroacetic
`acid (TCA)
`Fluoroacetic acid
`(FA)
`Difluoroacetic
`acid (DFA)
`Trifluoroacetic
`acid (TFA)
`
`1.29
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`0.0513
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`2,900
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`0.65
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`0.224
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`13,000
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`I 2.66
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`0.00219
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`J 126
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`1.24
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`0.0575
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`3,300
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`0.23
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`0.589
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`33,850
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`Source: H.C. Brown, D.H. McDaniel, and O.Haflinger, "Determination of
`
`Organic Structures by Physical Methods, Vol. 1" E.A. Braude and F .C.
`
`Nachold, Eds., Academic Press, NY, 1955, P. 567. This table and article is
`
`representative of the knowledge of POSA at the time.
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`35.Accordingly, TCA is about 4.5 times more acidic than DCA and DCA is
`
`about 2,900 times more acidic than acetic acid.
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`36.Fluoroacetic acid is not generally used because it is a deadly poison.
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`37.Chloroacetic acid and Trichloroacetic acid (TCA) are both solid at room
`
`temperature.
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`3 8. TF A and TCA are both corrosive substances.
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`39.Because peracid oxidations of sulfides and the characteristics of the above
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`carboxylic acids were known, much of the literature pertaining to sulfide
`
`oxidations is directed to selecting specific conditions that may be preferred
`
`in specific situations.
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`Interference No. 105,995
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`40. The extent of sulfide oxidation reactions reported in the literature by July
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`2010 would have permitted a POSA to predict the general outcome of a
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`sulfide oxidation reaction involving the halogenated derivatives of acetic
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`acid mentioned above.
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`5 Halogenated Acetic Acid Derivatives were Known in Sulfide Oxidations
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`41.US Patent No. 6,013,761 issued January 11, 2000 to Zierer et al. ("US
`
`'761") is entitled "Oxidation of Polyaryletie Sulfides" and relates to
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`methods of selectively oxidizing sulfide polymers to sulfoxides without
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`over-oxidation (i.e., selectivity). Ex. 1024.
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`42.US '761 discloses that the sulfide is oxidized in the presence of a
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`halogenated derivative of acetic acid and hydrogen peroxide. Id. at Col. 2,
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`II. 1-12.
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`43. US '7 61 discloses a list of preferred acids, which includes sulfuric acid,
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`TFA, TCA, and DCA. Id. at Col. 2, 11. 56-62.
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`44.Dichloroperacetic acid (DCPA) is mentioned in US '761 as a particularly
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`preferred halogenated derivative of acetic acid for use with hydrogen
`
`peroxide. Id. at Col. 3, II. 1-12.
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`45.In several oxidation examples, US '761 uses DCA as the oxidation
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`medium, with hydrogen peroxide. Id. at Col. 7, Table 3. US '761
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`Interference No. 105,995
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`demonstrated the suitability ofDCA as an oxidation solvent, and identified
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`DCA as an alternative to TCA and TF A. Id. at Cols. 9-10.
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`46.US '761 is representative of the knowledge of a POSA at the time. A POSA
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`understood that a halogenated acetic acid when combined with hydrogen
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`peroxide forms a relatively strong peracid, which in turn would oxidize a
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`sulfide. Also consistent with common knowledge, the POSA would
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`recognize that the halogenated acids TF A, DCA, and TCA are all generally
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`interchangeable for the purpose of oxidizing a sulfide to make a sulfoxide,
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`even with their varying levels of acidity.
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`47.US Patent No. 3,928,372 issued December 23, 1975 to Bochis et al. ("US
`
`'372") relates to the preparation of certain biologically active compounds,
`
`and discloses their preparation, including oxidation of a thiazole sulfur
`
`atom on an organic molecule. Ex. 1014.
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`48.US '372 acknowledges that sulfur oxidation reactions,per se, were known,
`
`and proceeds to explain that suitable peracids for sulfur oxidation are those
`
`derived from organic acids having a pKa of less than 4.0. US '372
`
`identifies in the same passage trifluoroperacetic acid (TFPA) and
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`dichloroperacetic acid (DCPA) as preferred peracids for the sulfur
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`oxidation reaction. Id. at Col. 3, II. 46-53.
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`Interference No. 105,995
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`49. US '3 72 interchangeably uses dichloro- and trifluoro- acetic acid (DCA and
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`TFA) in its examples 1-8. Id. at Cols. 5-7.
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`SO.US '372 and US '761 are just two documents in the prior art that represent
`
`the knowledge of a POSA and confirm that the POSA would recognize that
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`although no two chemicals are identical, TF A, TCA, and DCA are
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`generally interchangeable and each would be expected to work in an
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`oxidation reaction producing fipronil from the sulfide compound 420.
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`1
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`2
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`5
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`6
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`8
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`9 Oxidations to Produce Fipronil with Halogenated Acetic Acid Derivatives were
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`10 Known
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`51. Fipronil is a pesticide compound that has been known for decades and is
`
`disclosed in US Patent No. 5,232,940 to Hatton et al. Exh. 1028, col. 132,
`
`line 23 to col. 133, line 54 and col. 146, lines 45-48. This patent is just
`
`one example representative of the knowledge of POSA at the time
`
`regarding the pesticidal applications of the fipronil compound.
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`52. It was known in the prior art that fipronil can be prepared by oxidizing the
`
`sulfide precursor Compound 420. Exh. 1019 at p.1, I. 1 to p.5, I. 5; Exh.
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`2001 at cols. 1-3; Exh. 2009 at p. 1, II. 4-19.
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`Interference No. 105,995
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`53.Based only on general knowledge in the art, as discussed above, a POSA
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`would have immediately considered hydrogen peroxide and a halogenated
`
`derivative of acetic acid for oxidation of Compound 420.
`
`54. The POSA would also know that peracids are more reactive oxidants than
`
`peroxides and would be well aware that peracetic acid has long been known
`
`to oxidize sulfides.
`
`55.Moreover, the POSA would know that a stronger derivative of acetic acid
`
`would cause the oxidation to fipronil to proceed more quickly and at lower
`
`temperature.
`
`56.There is a finite group of such compounds that would be considered by the
`
`POSA. In this regard, an obvious choice would have been a halogenated
`
`derivative of acetic acid, because these are commercially available and are
`
`stronger acids than non-halogenated carboxylic acids. They are also known
`
`to be oxidized into halogenated peracids with H20 2• Examples are found in
`
`the literature such as Exs. 1018, 2009.
`
`57.Chloroacetic acid and Trichloroacetic acid (TCA) are both solid at room
`
`temperature and would require a cosolvent. TCA is also very corrosive and
`
`expensive.
`
`58.However, DCA is conveniently a liquid at room temperature, less
`
`expensive, and less corrosive, making it an obvious choice among the set of
`
`15
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`
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`1
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`2
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`3
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`4
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`5
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`18
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`19
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`20
`
`Interference No. 105,995
`
`possible halogenated derivatives of acetic acid that a POSA would
`
`consider.
`
`59.The fluorinated carboxylic acids would be disfavored because they are only
`
`slightly more acidic than the chloro counterparts but tend to be expensive,
`
`toxic, and highly corrosive.
`
`60.It was also known to the POSA that a strong acid such as sulfuric acid
`
`could be used to increase the oxidation reaction rate when using a weaker
`
`peracid, as acknowledged by Dr. Trost. Ex. 2003,, 39.
`
`61.As the oxidation reaction of Compound 420 is well known, prior literature
`
`pertaining to oxidation of Compound 420 to fipronil is concerned in large
`
`part with selecting conditions that may improve commercial scale
`
`production of fipronil.
`
`62.For example, a POSA would know the content of WO 01/30760 Al ("WO
`
`'760"), published in 2001, describing the preparation of fipronil by
`
`oxidation with trifluoroperacetic acid prepared from TF A and hydrogen
`
`peroxide, and further describing such preparation as giving "excellent
`
`results in terms of both selectivity and yield." Ex. 1019 at page 2, lines 6-8
`
`and page 7, line 19 to page 8, line 2; Example 1 on pages 16-17.
`
`63.WO '760 states that the use ofTFA and hydrogen peroxide (forming
`
`trifluoroperacetic acid in situ) for the oxidation of sulfides to sulfoxides
`
`16
`
`
`
`Interference No. 105,995
`
`and/or sulfones is known and generally useful for the oxidation of electron
`
`deficient sulfides. Id. at p.1.
`
`64.However, WO '760 states that a problem encountered in oxidizing 5-
`
`amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-
`
`trifluoromethylthio pyrazole in the presence ofTFA is the coformation of
`
`the corresponding sulfone due to over-oxidation. Id. at p. 1.
`
`65.Representative of the knowledge of a POSA, WO '760 states that a number
`
`of oxidants (including sodium vanadate, sodium tungstate, peracetic acid,
`
`performic acid and pertrichloroacetic acid) have been employed to attain an
`
`efficient and regioselective oxidation suitable for large scale preparations of
`
`fipronil, but were found to be unsatisfactory in one respect or another. Id.
`
`at pp. 1-2. Thus, the POSA was aware of multiple examples of fipronil
`
`production, each having its own suitability for a given purpose, but all
`
`resulting in fipronil.
`
`66.While WO '760 states that use ofTFA with hydrogen peroxide
`
`(trifluoroperacetic acid) gives excellent results in terms of yield of fipronil
`
`(Id. at p. 2, II. 6-8), WO '760 also confirms, representative of the
`
`knowledge of POSA, that a much weaker carboxylic acid, peracetic acid
`
`(i.e. acetic acid) can also be used to form fipronil. Id. at p.1, I. 30.
`
`1
`
`2
`
`3
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`4
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`5
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`6
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`7
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`8
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`9
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`11
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`12
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`13
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`14
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`15
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`16
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`17
`
`18
`
`19
`
`20 WO 2007/122440 Al Discloses all of the Elements of Claim 1 of the '559 Patent
`
`17
`
`
`
`Interference No. 105,995
`
`67.WO 2007/122440 Al, which is entitled "Process for the Preparation of
`
`Fipronil, an Insecticide, and Related Pyrazoles" ("WO '440"), published in
`
`2007, discloses a fipronil preparation process. Ex. 2009.
`
`68.At page 1, WO '440 refers to WO '760 and explains that this known
`
`commercial process for the manufacture of fipronil uses corrosive and
`
`expensive chemicals such as trifluoroacetic acid (TF A), presenting a
`
`problem in the art. Ex. 2009.
`
`69.WO '440 proposes one approach for solving this problem by substituting
`
`the corrosive and expensive solvent trifluoroacetic acid (TFA) with an
`
`alternative solvent. (Id. at p. 1).
`
`70. WO '440 suggested that TCA can be an effective solvent for the oxidation
`
`when used with a suitable melting point depressant. (Id. at p. 2). WO '440
`
`reported a commercially viable oxidation of the sulfide precursor into
`
`fipronil using a mixture of 70-80% TCA and 30-20% DCA together with
`
`hydrogen peroxide. (Id. at pp. 12-14, claim 9, including claims 1-8 on
`
`which it may depend; Ex. 2001 at col. 2, ll. 38-42)
`
`71.WO '440 summarizes the art offipronil production and explains that
`
`oxidants such as peracids, peroxides, and persulfates have been widely used
`
`for performing oxidation reactions where stability under the oxidation
`
`1
`
`2
`
`3
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`4
`
`5
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`6
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`8
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`9
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`12
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`14
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`18
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`19
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`18
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`
`
`1
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`2
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`3
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`4
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`5
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`6
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`7
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`8
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`9
`
`IO
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`11
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`13
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`14
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`15
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`16
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`17
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`18
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`19
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`20
`
`Interference No. 105,995
`
`conditions, unreacted starting material, and over-oxidation are
`
`considerations. (Id. at pp. 4-5).
`
`72.Because trichloroacetic acid (TCA) is solid under certain conditions, WO
`
`'440 suggests mixing TCA with at least one melting point depressant,
`
`preferably dichloracetic acid (DCA). (Id. at p. 7).
`
`73 .Example 1 (p. 10) of WO '440 discloses a process meeting every element
`
`of claim 1 except that TCA is present in admixture with DCA. Example 1
`
`represents a preferred embodiment in WO '440.
`
`74. WO '440 also disclosed that DCA is itself a medium for fipronil oxidation,
`
`and acidic enough to do so. (Id. at p. 9, II. 15-23).
`
`75.In discussing DCA, WO '440 explained that "the preferred melting point
`
`depressant [DCA] is a poor medium for oxidation and the purpose of its
`
`addition is only to sufficiently depress the melting point of trichloroacetic
`
`acid to facilitate ease of processing." (Id. at p. 9).
`
`76.The term "medium for oxidation" must refer to fipronil preparation because
`
`WO '440 only discusses fipronil preparation by oxidation.
`
`77. The POSA would understand the disclosure on page 9 to mean that DCA is
`
`a poor medium as compared to the TCA/DCA mixture preferred by WO
`
`'440 for preparing fipronil by oxidation, possibly based on the lower
`
`acidity ofDCA comparedto TCA.
`
`19
`
`
`
`Interference No. 105,995
`
`78.However, the POSA would also know that DCA is a relatively strong acid.
`
`As explained above, DCA was a known oxidant, only about 4.5 times less
`
`acidic than TCA.
`
`79.The POSA would understand from WO '440, including page 9, that DCA is
`
`a poor medium for oxidation of fipronil but one that would nevertheless
`
`produce fipronil. In fact, claim 1 of the '559 patent covers the use of any
`
`medium: including the "poor medium" DCA when not used in mixture with
`
`TCA and/or TCP A.
`
`80.Because the POSA would have known that DCA is not as strong as TFA or
`
`TCA, the POSA would have sought to make DCA a stronger oxidizing
`
`agent, including by addition of strong acid, e.g. sulfuric acid, which would
`
`make DCA a considerably stronger oxidizing agent. Thus, merely
`
`conventional skill would have led the POSA to add a strong acid, e.g.
`
`sulfuric acid, in place of the TCA in the process of WO '440, for the
`
`purpose of accelerating the oxidation process.
`
`81. The below claim chart indicates each element of claims 1-12 and its
`
`corresponding disclosure in WO '440.
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
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`9
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`10
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`11
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`12
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`15
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`16
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`17
`
`Claim 1 of U.S. Patent No.
`8,304,559 B2
`
`W02007/122440 Al Disclosure
`
`20
`
`
`
`Interference No. 105,995
`
`(reorganized so that the structure of
`general formula (II) immediately
`I follows the introduction of the
`compound having the general
`1 formula (11))
`
`I
`
`A method for the preparation of the W02007 /122440 page 10, lines 24-
`compound having the following
`2 5 (Example 1):
`general formula (I):
`
`F3C
`\s~o
`
`NC
`
`K
`
`°"N
`
`NH2
`
`R1
`
`R2
`
`~ I
`
`~
`
`CF3
`
`(I)
`
`wherein R I and R2 are independently
`hydrogen or halogen;
`
`I
`
`I
`
`"(95% yield). HPLC determination
`by an internal standard method
`showed the solid to be 92% pure."
`
`W02007/122440 page 2, line 24 to
`page 3, line 6:
`
`"The present invention relates to
`improved oxidation process for
`preparing 5-amino-1-phenyl-3-
`cyano-4-trifluoromethyl sulphinyl
`pyrazole pesticides as defined by
`formula-I
`
`below.
`
`21
`
`
`
`Interference No. 105,995
`
`{Formula-I)
`
`wherein,
`
`R1 = trifluoromethyl or
`trifluoromethoxy
`
`R2, R3 = individually hydrogen,
`chlorine or bromine"
`
`W02007/122440 page 10, lines 1-5
`
`"In a preferred embodiment of the
`process of the present invention R1 =
`trifluoromethyl and R2, R3 =
`chlorine, the process therefore
`resulting in the production of 5-
`amino-1-
`
`(2, 6-dichloro-4-
`trifluoromethylphenyl) -3-cyano-4-
`trifluoromethyl sulphinyl pyrazole
`(Fipronil)."
`
`W02007/122440 page 10, lines 10-
`25 (Example 1):
`
`22
`
`through oxidation of a compound
`having the general formula (11)
`
`
`
`(II)
`
`wherein R1 and R2 are defined as
`above,
`
`Interference No. 105,995
`
`"[A] solvent mixture, containing 700
`ml trichloroacetic acid and 3 00 ml
`dichloroacetic acid, was added to a
`flask and 421 g (1 g mole) of 5-
`amino-1-(2,6-dichloro-4-
`trifluoromethylphenyl)-3-cyano-4-
`tdflu_Qromethylthio pyrazole was
`dissolved in it." (emphasis added.)
`
`W02007/122440 page 3, lines 7-12:
`
`"which process comprises the step of
`oxidizing a compound of formula-II.
`
`C"hCN
`
`H2N N
`~
`
`~
`
`R1
`(Formula-II)
`
`wherein,
`
`Rl = trifluoromethyl or
`trifluoromethoxy
`
`R2, R3 = individually hydrogen,
`chlorine or bromine"
`
`23
`
`
`
`Interference No. 105,995
`
`in the presence of dichloroacetic acid W02007/122440 page JO, lines 10-
`18 (Example 1):
`
`"[A] solvent mixture, containing 700
`ml trichloroacetic acid and 300 ml
`dichloroacetic acid, was added to a
`flask"
`
`W02007/122440 page 9, lines 17-
`23:
`
`"[T]he preferred melting point
`depressant dichloro acetic acid is a
`poor medium for oxidation and the
`purpose of its addition is only to
`sufficiently depress the melting point
`of trichloro acetic acid to facilitate
`ease of processing. 20-30% by
`weight content of dichloro acetic
`acid in the trichloroacetic acid is
`generally sufficient to achieve this
`objective." (emphasis added.)
`
`and of an oxidising agent[,]
`where the oxidising agent is selected wo2oo7!l22440 page 10, lines 10-
`2 5 (Example 1):
`from the group comprising benzoyl
`peroxides, sodium peroxides, t-butyl
`"[A] solvent mixture, containing 700
`peroxides and/or hydrogen peroxide, ml trichloroacetic acid and 300 ml
`dichloroacetic acid, was added to a
`flask and 421 g (1 g mole) of 5-
`amino-1-(2,6-dichloro-4-
`trifluoromethylphenyl)-3-cyano-4-
`
`24
`
`
`
`Interference No. 105,995
`
`trifluoromethylthio pyrazole was
`dissolved in it. After stirring ... ,
`hydrogen peroxide solution ... was
`added." (emphasis added.)
`
`W02007/122440 page 4, lines 6-10:
`
`teaching that the "more preferred"
`oxidizing agents are "peroxides, in
`particular benzoyl peroxide, sodium
`peroxide, tert butyl peroxide and
`hydrogen peroxide, the most
`preferred oxidizing agent being
`hydrogen peroxide."
`
`and wherein the oxidation is
`conducted in the absence of
`trichloroacetic acid and/or
`trichloroperacetic acid.
`
`i
`Claim 2 of U.S. Patent No.
`8,304,559 B2
`
`The method according to claim 1,
`
`wherein R 1 and R2 are chlorine or
`bromine.
`
`W02007/122440 page 9, lines 17-
`23:
`
`"[T]he preferred melting point
`depressant dichloro acetic acid is .. ~
`poor medium for oxidation ... "
`reaction producing fipronil.
`( emphasis added.)
`
`W02007/122440 page 10, lines 1-5
`
`I
`
`"In a preferred embodiment of the
`process of the present invention R1 =
`I trifluoromethyl and R2, R3 =
`I chlorine, the process therefore
`resulting in the production of 5-
`amino-1-(2, 6-dichloro-4-
`trifluoromethylpheny 1 )-3-cyano-4-
`
`I
`
`I
`I
`t
`I
`l
`!
`
`25
`
`
`
`Claim 3 of U.S. Patent No.
`8,304,559 B2
`
`The method according to claim 1,
`
`wherein the compound having the
`general formula (I) is 5-amino-1-
`(2,6-dichloro-4-trifluoromethyl-
`phenyl)-4-trifluorometansulfinyl-lH-
`pyrazole-3-carbonitrile.
`
`Interference No. 105,995
`
`trifluoromethyl sulphinyl pyrazole
`(Fipronil)."
`
`-also claim 15 of WO '440
`
`W02007/122440 page 10, lines 1-5
`
`"In a preferred embodiment of the
`process of the present invention Rl =
`trifluoromethyl and R2, R3 =
`chlorine, the process therefore
`resulting in the production of 5-
`amino-1-(2, 6-dichloro-4-
`trifluoromethylpheny 1 )-3-cyano-4-
`trifluoromethyl sulphinyl pyrazole
`(Fipronil)."
`
`-also claim 15 of WO '440
`
`Claim 4 of U.S. Patent No.
`8,304,559 B2
`
`W02007/122440 page 9, lines 17-
`23:
`
`The method according to claim 1,
`
`wherein the dichloroacetic acid is
`oxidised to dichloroperacetic acid
`through the oxidising agent.
`
`"[T]he preferred melting point
`depressant dichloro acetic acid is a
`poor medium for oxidation ... "
`reaction producing fipronil.
`( emphasis added.)
`
`W02007/122440 page 10, lines 10-
`2 5 (Example 1):
`
`"[A] solvent mixture, containing 700
`ml trichloroacetic acid and 300 ml
`dichloroacetic acid, was added to a
`flask and 421 g (1 g mole) of 5-
`amino-1-(2,6-dichloro-4-
`trifluoromethylphenyl)-3-cyano-4-
`trifluoromethylthio pyrazole was
`
`26
`
`
`
`I
`
`Interference No. 105,995
`
`dissolved in it. After stirring ... ,
`hydrogen peroxide solution ... was
`added." ( emphasis added.)
`
`Claim 5 of U.S. Patent No.
`8,304,559 B2
`
`W02007 /122440 page 9, lines 17-
`23:
`
`The method according to claim 4,
`
`wherein oxidation of the
`dichloroacetic acid takes place in
`situ.
`
`1 "[T]he preferred melting point
`depressant dichloro acetic acid is a
`£OOr medium for oxidation . .. "
`reaction producing fipronil.
`( emphasis added.)
`
`W02007 /122440 page 10, lines 10-
`2 5 (Example 1):
`
`"[A] solvent mixture, containing 700
`ml trichloroacetic acid and 300 ml
`dichloroacetic acid, was added to a
`flask and 421 g (1 g mole) of5-
`amino-1-(2,6-dichloro-4-
`trifluoromethylpheny 1 )-3-cyano-4-
`trifluoromet
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