EXHIBIT 1003
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`
`
`
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Exhibit 1003
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MERIAL 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-
`
`DECLARATION OF JAMES E. PATE, PhD,
`
`IN SUPPORT OF PETITION FOR INTER PARTES REVIEW OF
`
`US PATENT NO. 8,501,799
`UNDER 35 USC §§ 311-319 AND 37 CFR § 42.1-.80 & 42.100-.123
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`TABLE OF CONTENTS
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`INTRODUCTION & QUALIFICATIONS ............................................................. 1
`
`THE PERSON OF ORDINARY SKILL IN THE ART .......................................... 6
`
`CONSTRUCTION OF TERMS USED IN THE CLAIMS ..................................... 7
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`APPLICATION OF PRIOR ART TO THE ‘799 PATENT CLAIMS .................. 22
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`-1-
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`
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`JAMES E. PATE, PhD, under penalty of perjury, declares and says that:
`
`Introduction & Qualifications
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`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 1004 with the Petition. I understand that this Declaration is Exhibit 1003
`
`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.
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`1.3
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`I attained a Ph.D. in Physical Chemistry from Stanford University in
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`1987 and a BA. in Chemistry from SUNY-Binghamton in 1980. From 1987 to
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`1993, I was a Senior Research Chemist/Project Leader in Personal Care Research
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`at The Dow Chemical Company ("Dow"), Where I developed products for topical
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`administration, such as sunscreens. From 1994 to 2002, at Dow, I was the Research
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`Leader/Technical Leader of a group of ten researchers focused on developing
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`dispersion and emulsion technologies. From 2002 to 2007, at Elanco Animal
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`Health, Eli Lilly & Co., I was a Principal Research Scientist and Lead Formulator
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`for companion animal solid dosage forms. From 2007 to 2011, I was a Research
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`Scientist at Merial, where I was the Leader of a group developing dosage forms,
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`including topical dosage forms. I am Principal Scientist at Merial, where I lead a
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`team developing dosage forms, including topical, oral and injectable forms. I am
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`not receiving any additional compensation or consideration for providing this
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`Declaration. Neither my employment nor any compensation or consideration for
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`my employment depends on the outcome of the Petition or any Trial declared as a
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`result of the Petition.
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`1.4
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`In making this Declaration I also have reviewed the documents
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`Attachment B to the Petition, namely, Exhibits 1001-1020 as tabulated below:
`
`Evidence / Exhibits Relied Upon in Petition
`And Reviewed in Makin this Declaration
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`EXHIBIT #
`
`EXHIBIT NAME
`
`1001
`
`1002
`
`US Patent No. 8,501,799 (citation form:
`“the ‘799 natent” and/or Exhibit 1001
`
`File History of US Patent No. 8,501,799
`(citation
`form:
`identification
`to
`a
`particular paper and page thereof and/or
`Exhibit 1002
`
`1003
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`NEWYORK/#350854.l
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`
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`Declaration of Dr. James Pate re ‘799- Patent (citation form: “Pate Declaration
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`|
`
`” and/or Exhibit 1003
`
`
`
`
`Evidence / Exhibits Relied Upon in Petition
`And Reviewed in Makin this Declaration
`
`
`
`EXHIBIT NAME
`
`Curriculum Vitae of Dr. James Pate
`
`
`
`
`
`
`
`Huet et al, US Patent No. 6,426,333,
`issued January 30, 2002, and available
`against
`the ‘799 patent claims under
`pre—AIA 35 USC § 102(b)
`(citation
`
`form: “Huet ‘333 patent at
`” and/or
`Exhibit 1005
`
`
`
`
`
`
`
`
`
`
`EXHIBIT #
`
`
`
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`
`
`
`
`
`The Merck Index, Fourteenth Edition,
`Merck Research Laboratories, 2006,
`
`
`compound. 1124 (definition of Benzyl
`
`Alcohol) (citation form: “Merck Index
`
`
`at 1124” and/or Exhibit 1006
`
`
`
`
`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
`
`
`
`
`
`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
`
`
`
`
`
`
`
`
`
`
`
`
`
`The Merck Index, Fourteenth Edition,
`Merck Research Laboratories, 2006,
`compound 6038 (definition of Methyl
`Cellosolve® also known as Ethylene
`glycol monomethyl
`ether
`and
`2-
`Methoxyethanol) (citation form: “Merck
`
`
`Index at 603 8” and/or Exhibit 1009
`The Merck Index, Fourteenth Edition,
`
`Merck Research Laboratories, 2006,
`
`1010
`
`
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`
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`Evidence / Exhibits Relied Upon in Petition
`And Reviewed1n Makin this Declaration
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`E_XH___IBIT#
`
`
`
`EXH____I___BITNAME
`
`2-
`(definition of
`3750
`compound
`of
`ethoxyethanol
`also
`known
`as
`Ethylene
`glycol monoethyl
`ether)
`(citation form: “Merck Index at 3750”
`and/or Exhibit 1010
`
`The Merck Index, Fourteenth Edition,
`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 1011
`
`
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
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`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 1013
`
`Bonneau et a1, “Comparative Efficacy
`of Two Fipronil Spot-on Formulations
`Against
`Experrnimental
`Flea
`Infestations (Ctenocephalides felis)
`in
`Dogs, Vol. 8, No. l, 2010, Intern] Appl
`Res Vet Med, pp 1-620 (citation form:
`“Bonneau at
`” and/or Exhibit 1014
`
`US 2004/0254125 to Saito
`et
`211.,
`published December 16,2004 (citation
`form: Saito or Saito ‘ 125
`
`Sabnis et a1, “Topical formulations of
`metaflumizone lus amitraz to treat flea
`
`
`
`Evidence / Exhibits Relied Upon in Petition
`And Reviewed1n Makin this Declaration
`
`E__XHIBIT#
`
`
`
`_E____XHIBITNAME
`
`
`
`dogs,”
`on
`infestations
`tick
`and
`(2007)
`150
`Veterinary Parasitology
`196—202 (citation form: “Sabnis” and/or
`Exhibit 1016
`
`Sirinyan et a1 / Bayer Heathcare AG,
`WO 2008/080541, published July 10,
`2008,
`from International Application
`PCT/EP2007/010980,
`and
`available
`against
`the ‘799 patent claims under
`pre-AIA 35 USC §102(a) (citation form:
`“WO ‘541” and/or Exhibit 1017
`
`Sirinyan et a1, 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
`
`and
`equivalent
`language
`English
`translation of Exhibit 1017 (citation
`form: “US ‘387” and/or Exhibit 1018
`
`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 1019
`
`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 § 102(b)
`(citation form: “the Etchegaray ‘724
`atent” and/or Exhibit 1020
`
`1018
`
`1019
`
`1020
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`1.5
`
`I understand that the Petition asserts that claims 1-15 of the ‘799
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`patent are unpatentable as follows:
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`> Claims 1-15 are obvious in View of the Huet ‘333 patent (Exhibit 1005) in View
`
`of Saito ‘125 (Exhibit 1015), alone, or in further View of, Bonneau (Exhibit
`
`1014); and
`
`> Claims 1-15 are obvious in View of the Huet ‘333 patent (Exhibit 1005), either
`
`alone, or in View of Sirinyan W0 ‘541 (Exhibit 1017), as evidenced by the
`
`English language equivalent thereof, Sirinyan ‘387 publication (Exhibit 1018),
`
`alone, or in further View of, Bonneau (Exhibit 1014); and
`
`> Claims 1-15 are obvious in View of the Etchegaray ‘765 Patent (Exhibit 1019)
`
`in view of the Etchegaray ‘724 patent (Exhibit 1020),
`
`in View of Bonneau
`
`(Exhibit 1014), alone, or in further View of Saito ‘ 125 (Exhibit 1015).
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`1.6
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`In this Declaration I confirm the chemistry in the Petition, claim
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`construction, art interpretation and application of the above-listed documents as to
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`the ‘799 patent claims, and the education, training and experience of the Person of
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`Ordinary Skill in the Art with respect to the ‘799 patent claims.
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`The Person Of Ordinary Skill In The Art
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`2.
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`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
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`patent would have been a scientist with a good working knowledge of formulation
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`chemistry and parasitology. The person would have gained this knowledge through
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`at
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`least an advanced degree
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`(MS or PhD)
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`in chemistry, pharmacy or
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`pharmaceutical sciences, and at
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`least
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`three (3) years of practical working
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`experience making and testing chemical formulations; and that experience should
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`include interfacing with individual(s) having at
`
`least an advanced degree in
`
`parasitology and individual(s) having at least an advanced degree in toxicology.
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`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
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`ectoparasite; fleas, lice and ticks are examples of ectoparasites. A composition that
`
`combats ectoparasites is also called an ectoparasiticide. There are various types of
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`formulations for combatting ectoparasites, including dips, shampoos; sprays, which
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`are sprayed onto the exterior of the animal; pour on formulations which are applied
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`by pouring the formulation along the backline of the animal from the withers to the
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`tailhead; and spot-on formulations which are highly concentrated and applied to a
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`small localized region on the animal, typically between the shoulder blades, for
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`diffusion of the active ingredient over the animal’s skin. (See, e.g., Huet ‘333,
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`Exhibit 1005, 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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`ectoparasiticide formulation. The term “pharmaceutical composition” is not
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`defined it in the ‘799 patent.
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`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
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`in particular against fleas, may especially be in the form of liquid
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`compositions (pipettes) or solutions for applying to the skin, also known
`
`as “Spot-On solutions”, to be applied very easily,
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`in a single topical
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`application directly to the animal's skin, generally between the shoulder
`
`blades.
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`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
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`patent states that the “pharmaceutical composition” can “provide[] effective and
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`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.
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`Another subject of the present patent application is the use of a liquid
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`pharmaceutical composition as described previously for the preparation
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`of an antiparasitic veterinary medicament for topical application for
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`preventing (protecting) and/or treating flea infestations on pets,
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`in
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`particular on cats or dogs.
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`According to this use, said medicament is intended to be applied by
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`direct application to the animal's skin, on the shoulder blades or along a
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`dorsal line starting from the base of the tail and going up to the neck.
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`However, none of the ‘799 patent claims limit the pharmaceutical composition to
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`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
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`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.
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`3.6 Accordingly, prior art formulations that involve flpronil, 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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`patent claims were limited to a spot-on, they would be nonetheless obvious in View
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`of the prior art, as herein discussed, and in the Petition.
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`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
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`“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
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`patent claims are intended to additionally include ivermectin, as in the Huet ‘333
`
`patent Examples 1 and 2 which involve both fipronil and ivermectin.
`
`5.
`
`“S-amino-l-[2,6-dichloro—4-(trifluoromethyl)phenyl]-4-
`
`(trifluoromethylsulfinyl)—1H-pyrazole-S-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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`arylpyrazole derivatives”. Fipronil in the claims means “5-amino-1-[2,6—dichloro-
`
`4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulf— inyl)-lH—pyrazole-3 -carbonitrile
`
`(fipronil)”;
`
`that
`
`is
`
`the phenylpyrazole or arylpyrazole or
`
`l-N-arylpyrazole
`
`derivative known as “fipronil”. (Huet ‘333 patent, Exhibit 1005, 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
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`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 m1 of the
`
`pharmaceutical composition.
`
`6.1
`
`Benzyl alcohol is the compound having the fomula:
`
`(Merck Index at 1124, Exhibit 1006.)
`
`be.
`
`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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`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 (PGME) means the compound
`
`having the structure:
`
`OH
`
`/l\/o\
`
`. 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 r0 anal and is also
`
`called: l—methoxy—Z-propanol. Pro lene 1 col monometh l ether is structural]
`
`
`
`considered both an ether and an alcohol havin our carbon atoms. (DOWANOL
`
`PM, Exhibit 1007.)
`
`7.2 Dipropylene glycol n—butyl ether (DPGBE) means the compound
`
`having the structure:
`
`)VOWAOM . Dipropylene glycol n-bufll
`
`ether has a h dro l mu and is also a ro anol derivative. Dipropylene glycol
`
`n-butyl ether is also called: 1-(l-butoxy-2-propoxy)-2-propanol; 2-Propanol, 1-(2-
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`1 2
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`
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`butoxy- 1 -methylethoxy)-;
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`and
`
`1—(2-Butoxy- 1 -methylethoxy)propan-2-ol.
`
`(DOWANOL DPnB , Exhibit 1008.)
`
`7.3
`
`Ethylene glycol monomethyl ether (EGME) means the compound
`
`having the structure:
`
`H0/\/ \. Ethanol is a C2 alcohol. Ethylene
`
`0
`
`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 1009.)
`
`7.4
`
`Ethylene glycol monoethyl ether (EGEE) means the compound having
`
`the structure: HO/VOV. 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 1010.)
`
`7.5 Diethylene glycol monoethyl ether (DEGME) means the compound
`
`having the structure:
`
`Ho/\/O\/\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
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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 1011.)
`
`7.6
`
`Propylene glycol (PG) means the compound having the structure:
`
`OH
`
`OHX/ . Propylene glycol has three carbon atoms and two hydroxyl groups.
`
`Propylene glycol is also called propane diol. Propplene glycol is a C: alcohol.
`
`(Merck Index at 7855, Exhibit 1012.)
`
`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 interpretation at the term “C1-C4 alcohol”
`
`encompasses compounds recited as the organic solvent in ‘799 pattent claim 1.
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`8.1
`
`“Alcohol” is defined as:
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`A broad class of hydroxyl-containing organic compounds
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`summarized
`
`as follows:
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`NEWYORK/#350854.l
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`14
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`
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`I.. Monohydric (1 OH group)
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`II. Dihydric (2 OH groups): glycols and derivatives (diols)
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`III. Trihydric (3 OH groups): glycerol and derivatives
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`IV. Polyhydric
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`(3 or more OH groups).
`
`(Hawley at 30-31, Exhibit 1013.)
`
`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
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`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 1002,
`
`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
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`NEWYORK/#350854.l
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`15
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`
`
`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 1002), and hence the patentee’s
`
`arguments do not distinguish “C1-C4 alcohol” from the “organic solven ” 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 1002), this does not limit
`
`the claim as the genus “C1-C4 alcohol” is not explicitly limited by, in or through
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`NEWYORK/#350854.l
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`16
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`
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`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 1013, Le, 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
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`NEWYORK/#350854.l
`
`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 1013, 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 cannot 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 1014). 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 scope of the
`
`NEWYORK/#350854.1
`
`18
`
`
`
`‘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 1001).
`
`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.
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`NEWYORK/#350854.l
`
`1 9
`
`
`
`8.8.5 Furthermore, with regard to the comparison between Effipro®
`
`(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 1002)), Bonneau (Exhibit 1014), at 19-20, states
`
`(with footnotes omitted, and emphasis added):
`
`Effipro® 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 yrotection is unlikely. Hence the
`
`information on both groducts’ data sheets which indicate that the
`
`insecticidal efficacy against new infestations with adult fleas Qersists
`
`for ug to eight weeks. Furthermore, recommendations of monthly
`
`agglications are commonly made, based on Qrevious field studies. ...
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`NEWYORIO#350854.1
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`20
`
`
`
`The present study shows that desgite different vehicles,
`
`the two
`
`formulations were equally able to eradicate flea infestation, and
`
`Qrevent new infestations. They were also egually well-tolerated.
`
`8.8.6 In short, Bonneau (Exhibit 1014) 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/#350854.1
`
`2 1
`
`
`
`of) odor of the formulation can also be an important characteristic. In this regard, I
`
`direct attention to Figures 1-7 of Sabnis (Exhibit 1016) 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 flpronil—
`
`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
`
`1005), Sirinyan WO ‘541 (Exhibit 1017), the Sirinyan ‘387 publication (Exhibit
`
`1018), the Etchegaray ‘765 Patent (Exhibit 1019),
`
`the Etchegaray ‘724 patent
`
`(Exhibit 1020), Saito ‘125 (Exhibit 1015) and Bonneau (Exhibit 1014) in the
`
`Petition.
`
`9.1
`
`I agree that it would have been obvious to replace the co-solvent
`
`methanol, ethanol or propanol of the Huet ‘333 patent (Exhibit 1005), e.g. Huet
`
`‘333 patent Example 1 or 2, with benzyl alcohol as Saito ‘ 125 teaches that ethanol,
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`NEWYORK/#350854.1
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`22
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`
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`isopropanol
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