UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Exhibit 1003A
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`1\/[ERIAL LIMITED,
`
`Petitioner,
`
`V.
`
`VIRBAC,
`
`Patent Owner.
`
`Patent No. 8,501,799
`
`Issue Date: August 6, 2013
`Title: PHARMACEUTICAL COMPOSITION CONTAINING
`
`AN N—PHENYPYRAZOLE DERIVATIVE, AND USE THEREOF
`FOR PREPARING A TOPICAL VETERINARY FOR FLEA CONTROL
`
`Case IPR: IPR2014-01279
`
`REVISED DECLARATION OF JAMES E. PATE, PhD,
`IN SUPPORT OF PETITION FOR INTER PARTES REVIEW OF
`
`UNDER 35 USC §§ 311-319 AND 37 CFR § 42.1-.80 & 42.100-.123
`
`US PATENT NO. 8,501,799
`
`NEWYORK/#355287.l
`
`Exhibit 1003A
`
`Merial V. Virbac
`
`IPR2014-01279
`
`
`
`Exhibit 1003A
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`1\/[ERIAL LIMITED,
`
`Petitioner,
`
`V.
`
`VIRBAC,
`
`Patent Owner.
`
`Patent No. 8,501,799
`
`Issue Date: August 6, 2013
`Title: PHARMACEUTICAL COMPOSITION CONTAINING
`
`AN N—PHENYPYRAZOLE DERIVATIVE, AND USE THEREOF
`FOR PREPARING A TOPICAL VETERINARY FOR FLEA CONTROL
`
`Case IPR: IPR2014-01279
`
`REVISED DECLARATION OF JAMES E. PATE, PhD,
`IN SUPPORT OF PETITION FOR INTER PARTES REVIEW OF
`
`UNDER 35 USC §§ 311-319 AND 37 CFR § 42.1-.80 & 42.100-.123
`
`US PATENT NO. 8,501,799
`
`NEWYORK/#355287.l
`
`Exhibit 1003A
`
`Merial V. Virbac
`
`IPR2014-01279
`
`
`
`TABLE OF CONTENTS
`
`INTRODUCTION & QUALIFICATIONS ........................................................... .. 1
`
`THE PERSON OF ORDINARY SKILL IN THE ART ........................................ .. 6
`
`CONSTRUCTION OF TERMS USED IN THE CLAIMS ................................... .. 7
`
`APPLICATION OF PRIOR ART TO THE ‘799 PATENT CLAIMS ................ .. 22
`
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`-1-
`
`
`
`JAMES E. PATE, PhD, under penalty of perjury, declares and says that:
`
`Introduction & Qualifications
`
`1.
`
`I understand that this Declaration is being filed in the US Patent &
`
`Trademark Office (“USPTO”) in conjunction with a PETITION FOR INTER
`
`PARTES REVIEW OF US PATENT NO. 8,501,799 (“Petition”) by Merial
`
`Limited (“Merial”).
`
`1.1
`
`I have read and understood that Petition and concur with its contents,
`
`especially as herein~discussed.
`
`I understand that
`
`the Petition requests of the
`
`USPTO that a Trial be instituted concerning the invalidity of claims of US Patent
`
`No. 8,501, 799 (“the ‘799 patent”).
`
`1.2 My Curriculum vitae (“Cv”) is submitted herewith and I understand it
`
`is Exhibit lO04AA with the Petition. I understand that this Declaration is Exhibit
`
`lO03AA with the Petition. My Cv includes the publications on which I am named
`
`as an author or co-author for the past ten (10) years, and the matters in which I
`
`have given testimony as a witness in the past four (4) years.
`
`1.3
`
`I attained a Ph.D. in Physical Chemistry from Stanford University in
`
`1987 and a B.A. in Chemistry from SUNY-Binghamton in 1980. From 1987 to
`
`1993, I was a Senior Research Chemist/Project Leader in Personal Care Research
`
`at The Dow Chemical Company ("Dow"), where I developed products for topical
`
`administration, such as sunscreens. From 1994 to 2002, at Dow, I was the Research
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`
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`Leader/Technical Leader of a group of ten researchers focused on developing
`
`dispersion and emulsion technologies. From 2002 to 2007, at Elanco Animal
`
`Health, Eli Lilly & Co., I was a Principal Research Scientist and Lead Formulator
`
`for companion animal solid dosage forms. From 2007 to 2011, I was a Research
`
`Scientist at Merial, where I was the Leader of a group developing dosage forms,
`
`including topical dosage forms. I am Principal Scientist at Merial, where I lead a
`
`team developing dosage forms, including topical, oral and injectable forms. I am
`
`not receiving any additional compensation or consideration for providing this
`
`Declaration. Neither my employment nor any compensation or consideration for
`
`my employment depends on the outcome of the Petition or any Trial declared as a
`
`result of the Petition.
`
`1.4
`
`In making this Declaration I also have reviewed the documents
`
`Attachment B to the Petition, namely, Exhibits 1001A-1020A as tabulated below:
`
`Evidence / Exhibits Relied Upon in Petition
`And Reviewed in Makin this Declaration
`
`EXHIBIT #
`
`EXHIBIT NAME
`
`
`
`1001A
`
`1002A
`
`1003A
`
`NEWYORK/#355287.l
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`US Patent No. 8,501,799 (citation fonn:
`“the ‘799 atent” and/or Exhibit 1001A
`
`File History of US Patent No. 8,501,799
`(citation
`form:
`identification
`to
`a
`particular paper and page thereof and/or
`
`Declaration of Dr. James Pate re ‘799
`
`Patent (citation form: “Pate Declaration
`
`
`
`
`
`
`
`
`EXHIBIT #
`
`Evidence / Exhibits Relied Upon in Petition
`And Reviewed in Makin this Declaration
`
`
`EXHIBIT NAME
`
`1004
`
`Curriculum Vitae of Dr. James Pate
`
`
`
`
`
`Huet et al, US Patent No. 6,426,333,
`1005
`
`issued January 30, 2002, and available
`against
`the ‘799 patent claims under
`pre-AIA 35 USC §
`l02(b)
`(citation
`form: “Huet ‘333 patent at ___” and/or
`Exhibit 1005A
`
`
`
`
`Merck Research Laboratories, 2006,
`compound. 1124 (definition of Benzyl
`
`Alcohol) (citation form: “Merck Index
`
`at 1124” and/or Exhibit 1006A
`
`
`
`Sheet
`Data
`Dow,
`“Technical
`DOWANOLTM PM,” Form No. 110-
`
`00617-0812, published 2012 (technical
`
`data sheet on “Propylene glycol methyl
`ether; 1-Methoxy-2-propanol”) (citation
`
`form: “DOWANOL PM” and/or Exhibit
`
`The Merck Index, Fourteenth Edition,
`
`
`
`
`
`
`
`Dow,
`“Technical
`Data
`Sheet
`DOWANOLTM DPnB,” Form No. Form
`
`No. 110-00620-0812, published 2012
`
`(technical data sheet on “Dipropylene
`glycol n-butyl ether”)
`(citation form:
`
`“DOWANOL DPnB” and/or Exhibit
`
`
`
`
`
`
`1008A)
`The Merck Index, Fourteenth Edition,
`Merck Research Laboratories, 2006,
`compound 6038 (definition of Methyl
`Ce1losolve® also known as Ethylene
`glycol monomethyl
`ether
`and
`2-
`
`Methoxyethanol) (citation form: “Merck
`
`Index at 603 8” and/or Exhibit 1009A
`1010
`The Merck Index, Fourteenth Edition,
`
`Merck Research Laboratories, 2006,
`
`
`
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`
`
`
`
`Evidence / Exhibits Relied Upon in Petition
`And Reviewed in Makin this Declaration
`
`EXHIBIT #
`
`EXHIBIT NAME
`
`
` compound
`
`
`
`3750
`
`(definition of 2-
`
`of
`as
`known
`also
`ethoxyethanol
`Ethylene
`glycol monoethyl
`ether)
`(citation form: “Merck Index at 3750”
`
`and/or Exhibit 1 010A
`
`The Merck Index, Fourteenth Edition,
`
`1011
`
`1012
`
`1013
`
`Merck Research Laboratories, 2006,
`compound 1800 (definition of Carbitol®
`also
`known
`as
`2-(2-
`Ethoxyethoxy)ethanol,
`Diethylene
`glycol monoethyl ether, and ethyl digol)
`
`
`(citation form: “Merck Index at 1800”
`
`and/or Exhibit 1011A
`
`The Merck Index, Fourteenth Edition,
`Merck Research Laboratories, 2006,
`compound
`7855
`(definition
`of
`Propylene
`glycol)
`(citation
`form:
`“Merck Index at 7855” and/or Exhibit
`
`
`
`
`
`
`
`
`
`
`
`
`“The Condensed Chemical
`Hawley,
`Dictionary,” 12th ed., pp 30-30 (1993)
`(definition of “alcohol”) (citation form:
`“Hawle at 30-31” or Exhibit 1013A
`
`
`
`
`1 014
`
`Bonneau et al, “Comparative Efficacy
`
`
`of Two Fipronil Spot-on Formulations
`Against
`Expermimental
`Flea
`
`Infestations (Ctenocephalides felis)
`in
`Dogs, Vol. 8, No. 1, 2010, Intern J Appl
`
`Res Vet Med, pp 16-20 (citation form:
`
`“Bonneau
`at
`”
`and/or Exhibit
`
`
`
`
`
`
`1015
`US 2004/0254125 to Saito
`et
`al.,
`published December 16, 2004 (citation
`
`form: Saito or Saito ‘ 125
`Sabnis et al, “Toical formulations o
` f
`
`
`1016
`
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`
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`
`
`EXHIBIT #
`
`Evidence / Exhibits Relied Upon in Petition
`And Reviewed in Makin this Declaration
`EXHIBIT NAME
`
`
`
`
`
`metaflumizone plus amitraz to treat flea
`and
`tick
`infestations
`on
`dogs,”
`Veterinary Parasitology
`1 50
`(2007)
`196-202 (citation form: “Sabnis” and/or
`Exhibit 1 0 16A
`
`
`
`Sirinyan et al / Bayer Heathcare AG,
`
`from International Application
`2008,
`PCT/EP2007/010980,
`and
`available
`
` WO 2008/080541, published July 10,
`
`
`
`
`
`
`
`
`
`
`
`1.5
`
`I understand that the Petition asserts that claims 1-15 of the ‘799
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`NEWYORK/#3 55287.1
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`
`
`
`
`
`
`
`
`
`
`
`
`
`
`the ‘799 patent claims under
`against
`pre-AIA 35 USC §102(a) (citation form:
`“WO ‘541” and/or Exhibit 1017A
`
`Sirinyan et al, Bayer Heathcare AG, US
`2009/0312387, published December 17,
`2009, from US application Serial No.
`12/520,169,
`filed as the US National
`
`
`
`
`
`
`
`
`
`
`
`
`
`Phase
`
`of
`
`PCT/EP2007/01980;
`
`an
`
`equivalent
`language
`English
`and
`translation of Exhibit 1017A (citation
`
`form: “US ‘387” and/or Exhibit 1018A
`
`
`Etchegaray, US Patent No. 6,395,765,
`issued May 28, 2002, and available
`against
`the ‘799 patent claims under
`
`
`pre—AIA 35 USC § 102(b)
`(citation
`
`form:
`“the Etchegaray ‘765 patent”
`and/or Exhibit 1019A
`
`
`al, US Patent No.
`Etchegaray et
`6,797,724, issued September 28, 2004,
`and available against
`the ‘799 patent
`claims under pre-AIA 35 USC § l02(b)
`(citation form: “the Etchegaray ‘724
`atent” and/or Exhibit 1020A
`
`
`1017
`
`1 01 8
`
`1 0 1 9
`
`1020
`
`
`
`patent are unpatentable as follows:
`
`> Claims 1-15 are obvious in View of the Huet ‘333 patent (Exhibit 1005A) in
`
`View of Saito ‘125 (Exhibit 1015A), alone, or in further View of, Bonneau
`
`(Exhibit 1014A); and
`
`> Claims 1-15 are obvious in View of the Huet ‘333 patent (Exhibit 1005A),
`
`either alone, or in View of Sirinyan W0 ‘541 (Exhibit 1017A), as evidenced by
`
`the English language equivalent thereof, Sirinyan ‘387 publication (Exhibit
`
`1018A), alone, or in fL11'thCI' View of, Bonneau (Exhibit 1014A); and
`
`> Claims 1-15 are obvious in View of the Etchegaray ‘765 Patent (Exhibit 1019A)
`
`in View of the Etchegaray ‘724 patent (Exhibit 1020A), in View of Bonneau
`
`(Exhibit 1014A), alone, or in further View of Saito ‘ 125 (Exhibit 1015A).
`
`1.6
`
`In this Declaration I confirm the chemistry in the Petition, claim
`
`construction, art interpretation and application of the above-listed documents as to
`
`the ‘799 patent claims, and the education, training and experience of the Person of
`
`Ordinary Skill in the Art with respect to the ‘799 patent claims.
`
`The Person Of Ordinary Skill In The Art
`
`2.
`
`From my education, training and experience, including as set forth
`
`herein and in my Cv, a person of ordinary skill in the art in the field of the ‘799
`
`patent would have been a scientist with a good working knowledge of formulation
`
`chemistry and parasitology. The person would have gained this knowledge through
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`NEWYORK/#355287.I
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`
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`at
`
`least an advanced degree
`
`(MS or PhD)
`
`in chemistry, pharmacy or
`
`pharmaceutical sciences, and at
`
`least
`
`three (3) years of practical working
`
`experience making and testing chemical formulations; and that experience should
`
`include interfacing with individual(s) having at
`
`least an advanced degree in
`
`parasitology and individual(s) having at least an advanced degree in toxicology.
`
`Construction Of Terms Used In The Claims
`
`3.
`
`The “Liquid Pharmaceutical Composition” Is NOT Limited To A
`
`“Spot-On”. A parasite that lives on the exterior of another animal is known as an
`
`ectoparasite; fleas, lice and ticks are examples of ectoparasites. A composition that
`
`combats ectoparasites is also called an ectoparasiticide. There are various types of
`
`formulations for combatting ectoparasites, including dips, shampoos; sprays, which
`
`are sprayed onto the exterior of the animal; pour on formulations which are applied
`
`by pouring the formulation along the backline of the animal from the withers to the
`
`tailhead; and spot-on formulations which are highly concentrated and applied to a
`
`small localized region on the animal, typically between the shoulder blades, for
`
`diffusion of the active ingredient over the animal’s skin. (See, e.g., Huet ‘333,
`
`Exhibit 1005A, at col. 1, 11. 34-65, col. 3, 11. 31-46.)
`
`3.1
`
`Claim 1 of the ‘799 patent calls for a liquid “pharmaceutical
`
`composition” and claims 2-14 are dependent, either directly or indirectly, on claim
`
`1.
`
`The term “pharmaceutical composition” is not
`
`typically used as to an
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`NEWYORK/#35 5287.1
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`ectoparasiticide formulation. The term “pharmaceutical composition” is not
`
`defined it in the ‘799 patent.
`
`3.2 With respect to “spot-on” formulations, the ‘799 patent, at column 2,
`
`lines 54-59 states:
`
`Specifically, products that are active against blood-sucking parasites, and
`
`in particular against fleas, may especially be in the form of liquid
`
`compositions (pipettes) or solutions for applying to the skin, also known
`
`as “Spot-On solutions”, to be applied very easily, in a single topical
`
`application directly to the animal's skin, generally between the shoulder
`
`blades.
`
`3.3
`
`In contrast,
`
`to the well-known terms, such as “shampoo”, “dip”,
`
`“spray”, “pour on” or “spot-on”, the ‘799 patent specification and claims use the
`
`undefined term “pharmaceutical composition.” At column 3, lines 36-39, the ‘799
`
`patent states that the “pharmaceutical composition” can “proVide[] effective and
`
`prolonged activity in treatment and protection
`
`in the form of a ready-to—use
`
`solution.” However,
`
`the ‘799 patent claims do not recite any “ready-to-use
`
`solution” and even if they did, that would not limit the claims to a “spot-on”
`
`formulation as other
`
`formulations,
`
`such as “dips”, “shampoos”, “pour on”
`
`formulations or “spray” formulations can be “ready-to-use.”
`
`3.4
`
`Similarly, at column 4, lines 38-49, the ‘799 patent reads:
`
`[T]he pharmaceutical composition is preferably conditioned in single-
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`dose pipettes.
`
`Another subject of the present patent application is the use of a liquid
`
`pharmaceutical composition as described previously for the preparation
`
`of an antiparasitic veterinary medicament for topical application for
`
`preventing (protecting) and/or treating flea infestations on pets,
`
`in
`
`particular on cats or dogs.
`
`According to this use, said medicament is intended to be applied by
`
`direct application to the animal's skin, on the shoulder blades or along a
`
`dorsal line starting from the base of the tail and going up to the neck.
`
`However, none of the ‘799 patent claims limit the pharmaceutical composition to
`
`being a formulation “in single—dose pipettes” for “direct application to the animal's
`
`skin, on the shoulder blades or along a dorsal line starting from the base of the tail
`
`and going up to the neck.”
`
`3.5
`
`The “pharmaceutical composition” of the ‘799 patent claims is not
`
`limited to being a “spot-on” formulation or a “pour-on” formulation.
`
`3.6 Accordingly, prior art formulations that involve fipronil, at least 5%
`
`(weight / volume) benzyl alcohol, and at least 50% (weight / Volume) of propylene
`
`glycol monomethyl ether, dipropylene glycol n-butyl ether, ethylene glycol
`
`monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl
`
`ether and propylene glycol, or mixtures thereof anticipate or render obvious the
`
`‘799 patent claims, as discussed herein and in the Petition. And even if the ‘799
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`
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`patent claims were limited to a spot-on, they would be nonetheless obvious in view
`
`of the prior art, as herein discussed, and in the Petition.
`
`4.
`
`The ‘799 Patent Claim 1 Phrase “Active Principle” Does NOT
`
`Limit the Composition To Only Containing Fipronil As An Active:
`
`I am
`
`advised and therefore believe that the term “comprising” has a particular meaning
`
`in US patent law; namely, that “comprising” is read as being inclusive or open-
`
`ended and does not exclude additional, unrecited elements or method steps. From
`
`this, I understand that the ‘799 patent claims allow for the presence of additional
`
`“active principles”. This is also borne out by claims 9 and 10 which call for “one
`
`or more additional antiparasitic active principles.” In this regard, the ‘799 patent
`
`specification, at col. 4, 11. 21-30 makes it clear that the compositions of the ‘799
`
`patent claims are intended to additionally include ivermectin, as in the Huet ‘333
`
`patent Examples 1 and 2 which involve both fipronil and iverrnectin.
`
`5.
`
`“5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-
`
`(trifluoromethylsulfinyl)-1H-pyrazole-3—carbonitrile (fipronil)” means the 1-
`
`N-arylpyrazole derivative known as “fipronil”: In the Field of the Invention,
`
`amongst other places, the ‘799 patent characterizes the genus of compounds that
`
`includes “fipronil” as “N-phenylpyrazole derivative[s].” A phenyl group is also
`
`known as an “aryl” group, and the genus of compounds that includes “fipronil” is
`
`also called “arylpyrazole derivatives” or “N-arylpyrazole derivatives” or “l-N-
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`NEWYORK/#355287. 1
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`10
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`
`
`arylpyrazole derivatives”. Fipronil in the claims means “5-amino-1-[2,6-dich1oro-
`
`4-(trifluoromethyl)phenyl]—4—(trifluoromethylsulf- inyl)- 1 H—pyrazole-3-carbonitrile
`
`(fipronil)”;
`
`that
`
`is
`
`the phenylpyrazole or arylpyrazole or 1-N-arylpyrazole
`
`derivative known as “fiproni1”. (Huet ‘333 patent, Exhibit 1005A, col. 2, 11. 52-57,
`
`col. 3, 1. 36, col. 8. L1. 30-36.)
`
`6.
`
`“At least 5% (weigh t/volume) of benzyl alcohol” has its ordinary
`
`meaning: The term “at least 5% (weight/Volume)” means that the concentration of
`
`benzyl alcohol present in the “pharmaceutical composition” is no less than 5% as a
`
`percentage based on “weight/volume” is a measure of concentration. In Example 1
`
`of the ‘799 patent, 30 g of benzyl alcohol is included in a formulation that contains
`
`10 g of fipronil, 0.02 g of buylhyroxyanisole (BHA), 0.01 g butylhydroxytoluene
`
`(BHT) and an amount of diethylene glycol monoethyl ether for the volume of the
`
`mixtue to be 100 ml (“qs 100 ml”). The concentration is thus in g/ml; “at least 5%
`
`(weight/volume)” means no less than 5 g benzyl alcohol per 100 ml of the
`
`pharmaceutical composition.
`
`6.1
`
`Benzyl alcohol is the compound having the fomula:
`
`(Merck Index at 1124, Exhibit 1006A.)
`
`7.
`
`“At least 50% (weight/volume) of an organic solvent chosen from
`
`propylene glycol monomethyl ether, dipropylene glycol n-butyl ether, ethylene
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`1 1
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`
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`glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol
`
`monoethyl ether and propylene glycol, and mixtures thereof” has its ordinary
`
`meaning: The term “at least 50% (weight/Volume)” means no less than 50 g of
`
`“propylene glycol monomethyl ether, dipropylene glycol n-butyl ether, ethylene
`
`glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol
`
`monoethyl ether[,] propylene glycol,
`
`[or] mixtures thereof’ per 100 ml of
`
`pharmaceutical composition.
`
`7.1
`
`Propylene glycol monomethyl ether (PGl\/IE) means the compound
`
`having the structure:
`
`OH
`
`JVON
`
`. Propylene glycol monomethyl ether
`
`has four carbon atoms, an oxygen, and a hydroxyl (OH) group. Propanol is a C3
`
`alcohol. Pro lene 1 col monometh l ether is a substituted ro anol and is also
`
`called: 1-methoxy-2-propanol. Pro lene 1 col monometh l ether is structural]
`
`
`
`considered both an ether and an alcohol havin our carbon atoms. (DOWANOL
`
`PM, Exhibit 1007A.)
`
`7.2 Dipropylene glycol n-butyl ether (DPGBE) means the compound
`
`having the structure:
`
`J\/‘W/\0/\/\ . Dipropylene glycol n-bu_t_zl
`
`ether has a h dro l mu and is also a ro anol derivative. Dipropylene glycol
`
`n-butyl ether is also called: 1-(1-butoxy-2-propoxy)-2—propanol; 2-Propanol,
`
`l—(2-
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`12
`
`
`
`butoxy— 1 -methylethoxy)-;
`
`and
`
`1 -(2-Butoxy— 1 —methylethoxy)propan—2-ol.
`
`(DOWANOL DPnB, Exhibit 1008A.)
`
`7.3
`
`Ethylene glycol monomethyl ether (EGME) means the compound
`
`having the structure: H0/\/\. Ethanol is a C2 alcohol. Ethylene
`
`glycol monomethyl ether has three carbon atoms, an oxygen, and a hydroxyl
`
`group. Ethylene glycol monomethyl ether is a substituted ethanol, as evidenced by
`
`it also being known as 2—Methoxyethanol, and Methyl Cellosolve®. Ethylene
`
`glycol monomethyl ether is structurally considered both an ether and an alcohol
`
`having three carbon atoms. (Merck Index at 6038, Exhibit 1009A.)
`
`7.4
`
`Ethylene glycol monoethyl ether (EGEE) means the compound having
`
`. /\/°\/
`the structure. HO
`
`. Ethylene glycol monoethyl ether has four
`
`carbon atoms, an oxygen and a hydroxyl group. Ethylene glycol monoethyl ether is
`
`also a substituted ethanol. Ethylene glycol monoethyl ether is also called 2-
`
`ethoxyethanol. EGEE is structurally considered both an ether and an alcohol with
`
`[our carbon atoms. (Merck Index at 3750, Exhibit 1010A.)
`
`7.5 Diethylene glycol monoethyl ether (DEGME) means the compound
`
`having the structure:
`
`HO/\/°\/\O/\
`
`. Diethylene glycol
`
`monoethyl ether has a hydroxyl group and is an ethanol derivative. Diethylene
`
`glycol monoethyl ether is also called 2-(2-Ethoxyethoxy)ethanol. It is a C2 alcohol
`
`NEWYORIU#355287.1
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`13
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`
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`derivative. It was, at the filing date of the ‘799 patent, also known as Transcutol.
`
`(Merck Index at 1800, Exhibit 1011A.)
`
`7.6
`
`Propylene glycol (PG) means the compound having the structure:
`
`OH
`
`/K/OH. Propylene glycol has three carbon atoms and two hydroxyl groups.
`
`Propylene glycol is also called propane diol. Progylene glycol is a C3 alcohol.
`
`(Merck Index at 7855, Exhibit 1012A.)
`
`7.7
`
`The term “and mixtures thereof’ is not defined in the ‘799 patent and
`
`means any mixture of any two or more of “propylene glycol monomethyl ether,
`
`dipropylene glycol n-butyl ether, ethylene glycol monomethyl ether, ethylene
`
`glycol monoethyl ether, diethylene glycol monoethyl ether and propylene glycol.”
`
`8.
`
`The phrase, “it being understood that said composition is free of
`
`C1-C4 alcohol” is nonsense and does not limit the ‘799 patent claims: While a
`
`skilled person would understand a C1 alcohol to be methanol, the entire term “C1—
`
`C4 alcohol” is NOT defined in the ‘799 patent; nor is “free of C1-C4 alcohol”.
`
`Moreover, the broadest reasonable intergretation of the term “C1-C4 alcohol”
`
`encomgasses comgounds recited as the organic solvent in ‘799 gattent claim 1.
`
`8.1
`
`“Alcohol” is defined as:
`
`A broad class of hydroxyl-containing organic compounds
`
`summarized
`
`as follows:
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`NEWYORlU#355287.1
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`14
`
`
`
`I.. Monohydric (1 OH group)
`
`II. Dihydric (2 OH groups): glycols and derivatives (diols)
`
`III. Trihydric (3 OH groups): glycerol and derivatives
`
`IV. Polyhydric
`
`(3 or more OH groups).
`
`(Hawley at 30-31, Exhibit 1013A.)
`
`8.2 Given, as discussed and illustrated above, that the claims explicitly
`
`call for at
`
`least 50% of the “pharmaceutical composition” to be an “organic
`
`solvent” selected from an alcohol having 3 or 4 carbon atoms, i.e., PG PGME,
`
`EGME, EGEE, or an alcohol
`
`that
`
`is an ethanol or propanol derivative,
`
`i.e.,
`
`DPGBE, DEGME, the phrase, “it being understood that said composition is free of
`
`C1-C4 alcohol” simply makes no sense. The problem is with the portion of the
`
`phrase reading, “C1-C4 alcohol”. As illustrated above, the term “C1-C4 alcohol”
`
`includes the organic solvent which is at
`
`least 50% of the entire claimed
`
`pharmaceutical
`
`composition. The phrase
`
`“it being understood that
`
`said
`
`composition is free of C1-C4 alcohol” is simply quite contrary to the plain language
`
`and chemistry of everything that appears before it in the claim. Indeed, the phrase
`
`is quite plainly diametrically opposed to everything that appears before it in the
`
`claim. Linguistically and chemically, it cannot be a limitation of the claims.
`
`8.3
`
`Looking for guidance to Exhibit 1003AA,
`
`the prosecution of US
`
`application Serial No. 13/132,996 (which matured into the ‘799 patent),
`
`in a
`
`February 13, 2013 Amendment, at 6-11, there appears to be diametrically opposed
`
`NEWYORK/#355287.l
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`15
`
`
`
`arguments presented to the Office.
`
`8.3.1 To attempt to distinguish US Patents Nos. 6,395,765 (“the ‘765
`
`patent”) and 6,797,724 (“the ‘724 patent”), the patentee characterized the claimed
`
`subject matter as “alcoholic solutions” and continued by asserting the recitation “it
`
`being understood that said composition is free of C1-C4 alcohol” to attempt to
`
`distinguish over those US Patents arguing that “comparative Examples 2, 3 and 4
`
`show an amazing and unexpected improvement of efficacy on flea infestation
`
`prevention
`
`compared to the well known commercial product Frontline®”, with
`
`the inference being that the supposed “amazing and unexpected improvement”
`
`arises from “it being understood that said composition is free of C1-C4 alcohol.”
`
`8.4
`
`The problem, of course, is that the “organic solvent” of the prior art
`
`‘765 patent overlaps with the “organic solvent” of the ‘799 patent claims (see
`
`September 14, 2012 Office Action; Exhibit l003AA), and hence the patentee’s
`
`arguments do not distinguish “C1-C4 alcohol” from the “organic solvent” of the
`
`‘799 patent claims.
`
`8.5 While the patentee argued, “US’724 does absolutely not deter from
`
`using C1-C4 alcohol: methanol, ethanol and isopropanol (i.e. C1-C4 alcohols) are
`
`listed among the organic solvents which can be used in oily compositions of
`
`US’724” (February 13, 2013 Amendment, at 7; Exhibit l003AA), this does not
`
`limit the claim as the genus “C1-C4 alcohol” is not explicitly limited by, in or
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`NEWYORK/#355287.1
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`1 6
`
`
`
`through the claim language of the ‘799 patent.
`
`8.5.1 It is also noted that the term “comprising” in the ‘799 patent
`
`claims allows an oily composition employing the excipients from the Etchagaray
`
`‘724 patent to be within the ‘799 patent claims.
`
`8.6 Moreover, the words, “methanol, ethanol and isopropanol” DO NOT
`
`appear anywhere in the ‘799 patent specification; they ARE NOT used by the
`
`patentee in the ‘799 patent specification to define, limit or even exemplify the
`
`genus “C1-C4 alcohol”.
`
`8.6.1 The ‘799 patent claims genus of “C1-C4 alcohol” is as broad as
`
`the term “alcohol”—e.g., the term encompasses “Dihydric (2 OH groups): glycols
`
`and derivatives (diols)”, Hawley at 30-31, Exhibit 1013A,
`
`i.e., compounds that
`
`make up at least 50% of the entire claimed pharmaceutical composition.
`
`8.7
`
`Linguistically and
`
`chemically under
`
`the broadest
`
`reasonable
`
`interpretation in View of the ‘799 patent’s specification,
`
`the phrase “it being
`
`understood that said composition is free of C1-C4 alcohol” cannot be a limitation of
`
`the ‘799 patent claims.
`
`8.8
`
`In the February 13, 2013 Amendment, the patentee asserted the data
`
`in Examples 2, 3 and 4 of the ‘799 patent as the basis to overcome obviousness in
`
`View of the ‘765 and ‘724 patents. That “data” fails to raise the language, “it being
`
`understood that said composition is free of C1-C4 alcohol” to being a claim
`
`NEWYORK/#3552871
`
`17
`
`
`
`limitation.
`
`8.8.1 There is absolutely no indication that the lack of the C1-C4
`
`alcohol is what is responsible for any alleged improvement; and there can be no
`
`such indication because as evidenced by Hawley at 30-31, Exhibit 1013A, the ‘799
`
`patent claims explicitly call for C1-C4 alcohols as the solvent that is at least 50% of
`
`the claimed pharmaceutical composition.
`
`8.8.2 Further,
`
`the
`
`‘799 patent claims
`
`are not
`
`limited to the
`
`composition in the ‘799 patent Examples; but are much broader in scope.
`
`Moreover, when evaluated in the light of the ‘799 patent assignee’s statements, the
`
`“data” in Examples 2, 3 and 4 of the ‘799 patent fails to demonstrate any actual,
`
`real world difference between the exemplified composition of the ‘799 patent and
`
`the prior art Frontline® composition. There carmot be extrapolation from only one
`
`study, especially across the entire scope of the ‘799 patent claims. The phrase “it
`
`being understood that said composition is free of C1-C4 alcohol” fails to provide
`
`the ‘799 patent with any distinction or difference over the prior art.
`
`8.8.3 More in particular,
`
`the “data” of the Examples of the ‘799
`
`patent was also published in Bonneau (Exhibit 1014A). The authors on Bonneau
`
`are from Virbac, ClinVet International (Pty) Ltd, and Groupe de Recherche
`
`Animaux de Compagnie. Composition A of the ‘799 patent Examples is called
`
`“Effipro®” in Bonneau. Composition A or Effipro® is not commensurate with the
`
`NEWYORK/#3552871
`
`18
`
`
`
`scope of the ‘799 patent claims.
`
`8.8.3.1
`
`The
`
`‘799 patent claims use the open-ended
`
`“comprising” transition, call for “at least 5% (weight/volume) benzyl alcohol, with
`
`the amount of fipronil unstated, the amount of the organic solvent being at least
`
`50%, and the organic solvent being possibly other
`
`than diethylene glycol
`
`monoethyl ether.
`
`8.8.3.2
`
`The ‘799 patent claims permit
`
`the amount of
`
`benzyl alcohol to be 25% less or about 19% more than that in Composition A.
`
`8.8.3.3
`
`Also, the ‘799 patent claims permit the organic
`
`solvent to be other than the diethylene glycol monoethyl ether of Composition A.
`
`8.8.3.4
`
`Further, the ‘799 patent claims permit there to be
`
`far less than 10% weight / volume fipronil used in Composition
`
`8.8.3.5
`
`A.
`
`Further
`
`still, with
`
`“comprising”,
`
`other
`
`ingredients than those recited, even in major amounts, may be present; see, e. g.,
`
`‘799 Patent, claims 9, 10 (Exhibit 1001A).
`
`8.8.4 For this reason———namely that Composition A or Effipro® is not
`
`commensurate with the scope of the ‘799 patent claims—that comparison
`
`(Composition A or Effipro®) provides no meaning to the phrase, “it being
`
`understood that said composition is free of C1-C4 alcohol”, and both should be
`
`disregarded.
`
`NEWYORK/#3552871
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`19
`
`
`
`8.8.5 Furthermore, with regard to the comparison between Eff1pro®
`
`(Composition A) and Frontline®, i.e., with respect to the “data” presented in the
`
`‘799 patent and argued by the patentee as somehow distinguishing over the prior
`
`art and showing that the phrase “it being understood that said composition is free
`
`of C1-C4 alcohol” provides some sort of distinction or difference (see February 13,
`
`2013 Amendment, at 8 (Exhibit 1003AA)), Bonneau (Exhibit 1014A), at 19-20,
`
`states (with footnotes omitted, and emphasis added):
`
`Eff1pro® Spot-on and Frontline® Top spot were both very effective
`
`treatments for flea infestation in dogs (efficacy of 99.7 and 100 percent
`
`respectively on day 2). This level of control is comparable to the efficacy
`
`of Frontline® Spot-on reported in various
`
`similar
`
`studies against
`
`experimental flea infestations in dogs or in semi-field studies.
`
`Under the conditions of this study, both treatments provided long-
`
`lasting residual protection against flea infestations
`
`. However, the
`
`standardized procedures,
`
`the absence of re-infestations
`
`from the
`
`environment or from other animals. the climatic stability, and the absence
`
`of bathing/swimming or other skin interventions. which could impair the
`
`diffusion of the product and/or its persistence on the skin. make the
`
`conditions of the present trial ideal. Therefore, under field conditions,
`
`such a long-lasting residual Qrotection is unlikely. Hence the
`
`information on both Qroducts’ data sheets which indicate that the
`
`insecticidal efficacy against new infestations with adult fleas Qersists
`
`or u
`
`to ei ht weeks. Furthermore recommendations 0 monthl
`
`agglications are commonly made, based on Qrevious field studies.
`
`NEWYORK/#3552871
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`20
`
`
`
`The present study shows that despite different vehicles,
`
`the two
`
`formulations were equally able to eradicate flea infestation, and
`
`grevent new infestations. They were also equally well-tolerated.
`
`8.8.6 In short, Bonneau (Exhibit 1014A) shows that: in reality there
`
`is no actual real world difference between that which is claimed in the ‘799 patent
`
`and that which is in the prior art; the “data” in the ‘799 patent does not distinguish
`
`the ‘799 patent claimed subject matter from that of the prior art, including because
`
`there is absolutely no indication that any lack of a C1-C4 alcohol is responsible for
`
`any alleged improvement by Effipro® in comparison with Frontline®; the phrase
`
`“it being understood that said composition is free of C1-C4 alcohol,” provides no
`
`difference or distinction between that which is claimed in the ‘799 patent and the
`
`prior art; and the phrase cannot be a limitation of the claims.
`
`8.8.6.1
`
`Indeed,
`
`I
`
`find it
`
`troubling that
`
`the implicit
`
`assumption in the ‘799 patent
`
`is that the only criterion for selection of the
`
`formulation is that it allegedly provided a benefit by extending the duration of
`
`efficacy for a limited time as compared to a commercial formulation because the
`
`selection of constituents for a formulation involves simultaneously balancing
`
`several Variables. Duration of efficacy is but one feature. However,
`
`it is also
`
`balanced against the important formulation characteristics such as deposition of
`
`crystalline material or an oily residue on the surface coat of the animal; and (lack
`
`NEWYORK/#355287.1
`
`21
`
`
`
`of) odor of the formulation can also be an important characteristic. In this regard, I
`
`direct attention to Figures 1-7 of Sabnis (Exhibit 1016A) which demonstrate the
`
`balancing of features to achieve a formulation. This is also recognized in the ‘799
`
`patent which, at column 2 lines 60 et seq, describes the propensity for fipronil to
`
`crystallize, and at column 10, lines 62 et seq, describes the failure of the ‘799
`
`patent formulation to overcome the propensity for fipronil to crystallize. Thus, the
`
`attempted “single attribute” (alleged extension of duration of efficacy) comparison
`
`of a single ‘799 patent formulation does not distinguish the genus of fipronil-
`
`containing formulations of the ‘799 patent claims from prior art fipronil-containing
`
`formulations.
`
`Application of Prior Art to the ‘799 Patent Claims
`
`9.
`
`I concur with and incorporate herein by reference as my herein
`
`statement the characterizations and application of the Huet ‘333 patent (Exhibit
`
`1005A), Sirinyan WO ‘541 (Exhibit 1017A),
`
`the Sirinyan ‘387 publication
`
`(Exhibit 1018A), the Etchegaray ‘765 Patent (Exhibit 1019A), the Etchegaray ‘724
`
`patent (Exhibit 1020A), Saito ‘125 (Exhibit 1015A) and Bonneau (Exhibit 1014A)
`
`in the Petition.
`
`9.1
`
`I agree that it would have been obvious to replace the co-solve
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