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`EXHIBIT 32
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`Page 1 of 110
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`SENJU EXHIBIT 2125
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`LUPIN v. SENJU
`IPR2015—0ll00
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`

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`DECLARATION QF ROBERT O. WILLIAMS, III
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`I.
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`QUALIFICATIONS
`
`1.
`
`I, Robert 0. Williams, III, Ph.D., submit this declaration at the request of Senju
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`Pharmaceutical Co., Ltd., Bausch & Lomb Incorporated and Bausch & Lomb Pharma Holdings
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`Corp. as an expert in the field of the design and evaluation of drug products. My qualifications
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`in these areas, as well as other areas, are established below and by my curriculum vitae, which is
`
`attached as Appendix A.
`
`2.
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`I am currently the Johnson & Johnson Centennial Chair of Pharmaceutics at the
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`University of Texas at Austin College of Pharmacy in Austin, Texas, where I have been teaching
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`and conducting research for over fifteen years. Also, I am the Division Head of Pharmaceutics.
`
`3.
`
`I received a B.S. degree in biology from Texas A&M University in 1979, a BS.
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`degree in pharmacy from the University of Texas at Austin in 1981, and a Ph.D. degree in
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`pharmaceutics from the University of Texas at Austin in 1986.
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`I am a licensed pharmacist.
`
`4.
`
`I have extensive experience and expertise in pharmaceutical formulation and the
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`use of excipients in formulating various types of drug dosage forms, including aqueous liquid
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`preparations.
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`I have experience with ophthalmic dosage forms including solutions.
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`I am an
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`expert in the field of pharmaceutical development, and I have worked almost exclusively in the
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`field of pharmaceutical development since 1986.
`
`5.
`
`Prior to becoming a professor, I worked in the pharmaceutical industry for several
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`companies including Rhone-Poulenc Rorer Pharmaceuticals, Duramed Pharmaceuticals and Eli
`
`Lilly and Company. Additionally, from 1996 to 2007 I was co-founder and President of
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`PharrnaForm, a contract pharmaceutical laboratory, and from 2007 to mid—20lO I was a director
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`of Akela Pharma.
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`I was the Chief Scientist from 2009 to 2013 and founder of Enavail, a particle
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`engineering contract services company. Accordingly, I have relevant industry experience in
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`addition to my academic qualifications.
`
`6.
`
`My current research focuses on the development, formulation, optimization and
`
`delivery of drugs by a variety of technologies, including aqueous liquid preparations.
`
`I have
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`extensive research experience and have authored numerous publications in this area.
`
`7.
`
`I have authored or co—authored over 400 published papers, abstracts and book
`
`chapters related to my Work in the pharmaceutical sciences. A significant number of my papers
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`are directed specifically to pharmaceutical formulation techniques and drug dosage forms.
`
`I am
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`a co-inventor on over 35 patents and/or patent applications that deal with drug formulation
`
`technology.
`
`8.
`
`Over the course of my career, I have earned numerous prestigious professional
`
`awards and honors, which are described on my curriculum vitae. For example, I was elected as a
`
`fellow to the American Association of Pharmaceutical Scientists and the American Institute of
`
`Medical and Biological Engineering.
`
`I have also received the William J. Sheffield Outstanding
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`Alumnus Award and was named a Dean’s Fellow at the University of Texas at Austin College of
`
`Pharmacy.
`
`9.
`
`I am currently the Editor-in-Chief for AAPS PharmSciTech, a joint publication of
`
`the American Association of Pharmaceutical Scientists and Springer Publishing.
`
`I was the
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`Editor-in-Chief for Drug Development and Industrial Pharmacy from 2000 to 2014.
`
`I am a
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`member of the Editorial Advisory Board for The Open Drug Delivery Journal.
`
`I also have
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`served or currently serve as a reviewer for many scientific journals,
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`including International
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`Journal of Pharmaceutics, Pharmaceutical Research, European Journal of Pharmaceutics and
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`Biopharmaceutics, Journal of the Controlled Release Society, S.T.P. Pharma, Pharmaceutical
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`Development and Technology, International Journal of Pharmaceutical Compounding, Journal
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`of Membrane Science, AAPS PharmSciTech, Journal of Pharmaceutical Sciences, Journal of
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`Pharmaceutical and Biomedical Analysis and Toxicology Letters.
`
`10.
`
`In addition to my research and teaching duties at the University of Texas at Austin,
`
`I have consulted for pharmaceutical, chemical and biotechnology companies.
`
`I have consulted
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`for both innovator pharmaceutical companies and generic pharmaceutical companies. Most of
`
`these consulting activities have dealt specifically with drug formulation issues.
`
`II.
`
`DOCUMENTS AND INFORMATION CONSIDERED IN FORMING OPINIONS
`
`11.
`
`I have been asked to provide my opinion on various terms and phrases in the
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`claims of U.S. Patent Nos. 8,129,431 (“the ’43l patent”), 8,669,290 (“the ’290 patent”),
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`8,754,131 (“the ’l3l patent”), 8,871,813 (“the ’813 patent”), and 8,927,606 (“the ’606 patent”)
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`(collectively, “the patents-in-suit”) as of the January 21, 2003, priority date of the patents-in-suit,
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`based on the knowledge and understanding of a person of ordinary skill in the art, and to respond
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`to certain proposed claim interpretations of Defendants.
`
`12.
`
`In forming my opinions, I have reviewed the patents-in-suit and their prosecution
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`histories.
`
`I also have considered the Joint Claim Construction and Prehearing Statement and the
`
`documents cited therein.
`
`I also have reviewed the declaration of Dr. Thomas Green.
`
`(Ex. I 37.)
`
`I additionally have based my opinions on my professional and academic experience in the areas
`
`of pharmaceutical development.
`
`I reserve the right
`
`to testify about
`
`these materials and
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`experience. To the extent I am provided additional documents or information, including any
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`declarations produced by Defendants, I may offer further opinions.
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`In addition to these materials,
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`I may consider additional documents and infomiation in forming any rebuttal opinions.
`
`1 “Ex. _” refers to the exhibits to the declaration of Bryan Diner in support of Plaintiffs’
`Opening Markman brief.
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`III.
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`LEGAL PRINCIPLES
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`13.
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`I have been informed and understand that the patent claims, and their terms and
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`phrases, are interpreted by the Court according to their ordinary and customary meaning to a
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`person of ordinary skill in the art at the time of invention. Iunderstand that interpreting a term or
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`phrase contained in a patent claim involves reading the language of the claim and considering
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`other materials relevant
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`to the claim,
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`including the patent specification and the prosecution
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`history.
`
`I understand that evidence extrinsic to the patent and its prosecution history may also
`
`be consulted, but that such materials should only be considered so long as they are not
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`inconsistent with the claim language, the patent specification and the prosecution history.
`
`14.
`
`I have been informed and understand that an independent patent claim does not
`
`itself refer to any other patent claim.
`
`I understand that a dependent patent claim refers to another
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`patent claim and incorporates all of the elements of the claim to which it refers, and also adds
`
`further elements.
`
`15.
`
`I have been informed and understand that
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`the transition phrase “consisting
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`essentially of” as it is used in a patent claim means that the claim encompasses the recited
`
`elements and only those non-recited elements that do not materially affect the basic and novel
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`properties of the claimed composition. As such, any non-recited element that materially affects
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`the basic and novel properties of the composition is excluded from the claim’s scope.
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`I further
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`understand that the transition phrase “consisting essentially of‘ differs from the open transition
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`term “comprising,” which means that the claimed composition is open to non-recited elements.
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`IV.
`
`STATEMENT OF OPINIONS EXPRESSED AND BASES AND REASONS
`THEREFORE
`
`A.
`
`Statement of Facts
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`16.
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`I understand that this litigation involves the ’431, ’290, ’13l, ’8l3, and ’606
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`patents, which cover Plaintiffs’ Prolensa® product. Prolensa® is an aqueous liquid preparation
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`containing bromfenacz sodium sesquihydrate as the active pharmaceutical ingredient.
`
`(Ex. 6 at 2
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`(“Description”).)
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`17.
`
`I understand that Defendants have each filed Abbreviated New Drug Applications
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`(“ANDAs”) with the U.S. Food and Drug Administration (“FDA”) to sell generic versions of
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`Prolensa® prior to expiration of the patents—in-suit. (Exs. 8-16.)
`
`1.
`
`The ’43l Patent Claims
`
`18.
`
`The claims of the ’431 patent are directed, generally speaking, to aqueous liquid
`
`preparations of bromfenac.
`
`(’431 patent at col. 11, line 65 — col. 14, line 22.) [understand that
`
`Defendants have raised claim construction disputes regarding certain claims of the ’431 patent.
`
`I
`
`understand that Plaintiffs have asserted that Defendants have infringed claims 1-4, 6-10 and 18-
`
`20 of the ’43l patent.
`
`19.
`
`Independent claim 1 of the ’431 patent is directed, generally speaking, to an
`
`aqueous liquid preparation consisting essentially of two components, where the first component
`
`is bromfenac or a pharmacologically acceptable salt or hydrate of bromfenac, where the hydrate
`
`is at least one selected from a 1/2 hydrate,
`
`1 hydrate and 3/2 hydrate, and where the second
`
`component is tyloxapol. The aqueous liquid preparation of claim 1 is formulated for ophthalmic
`
`administration.
`
`If a quaternary ammonium compound is included in the aqueous liquid
`
`preparation of claim 1, it is benzalkonium chloride (“BAC”).
`
`(’431 patent at col. 11, line 66 —
`
`col. 12, line 9.)
`
`2 The chemical name for bromfenac is 2-amino-3-(4-bromobenzoyl)phenylacetic acid.
`(’431 patent at col. 1, lines 24-36.)
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`20.
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`Dependent claim 2 of the ’43l patent
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`is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the first component is a bromfenac sodium salt.
`
`(’43l patent at col. 12, lines 10-12.)
`
`21.
`
`Dependent claim 3 of the ’431 patent
`
`is directed, generally speaking,
`
`to the
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`aqueous liquid preparation of claim 1, where the second component
`
`is tyloxapol and the
`
`pharmacologically acceptable salt of bromfenac is a sodium salt, the concentration of tyloxapol
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`is from about 0.01 w/v % to about 0.5 w/v %, the first component is a bromfenac sodium salt,
`
`and the concentration of the bromfenac sodium salt is from about 0.01 w/v % to about 0.5 w/v %.
`
`(’43l patent at col. 12, lines 13-23.)
`
`22.
`
`Dependent claim 4 of the ’431 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 3, where the concentration of tyloxapol is from about 0.01
`
`w/v % to about 0.3 w/v % and the concentration of the bromfenac sodium salt is from about 0.05
`
`to about 0.2 w/v %. (’431 patent at col. 12, lines 24-28.)
`
`23.
`
`Dependent claim 6 of the ’431 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 4, where the concentration of tyloxapol is about 0.02 w/v %.
`
`(’431 patent at col. 12, lines 32-34.)
`
`24.
`
`Dependent claim 7 of the ’431 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the fonnulation further includes one or more
`
`additives selected from the group consisting of a preservative, buffer,
`
`thickener, stabilizer,
`
`chelating agent, and pH controlling agent. (’431 patent at col. 12, lines 35-39.)
`
`25.
`
`Dependent claim 8 of the ’431 patent
`
`is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 7, where the preservative is benzalkonium chloride, the
`
`buffer is boric acid and/or sodium borate, the thickener is polyvinylpyrrolidone, the stabilizer is
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`sodium sulfite, the chelating agent is sodium edetate, and the pH controlling agent is sodium
`
`hydroxide. (’431 patent at col. 12, lines 40-46.)
`
`26.
`
`Dependent claim 9 of the ’431 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 8, where the pH is from about 7 to about 9.
`
`(’43l patent at
`
`col. 12, lines 47-48.)
`
`27.
`
`Dependent claim 10 of the ’43l patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 8, where the pH is from about 7.5 to about 8.5.
`
`(’431 patent
`
`at col. 12, lines 49-50.)
`
`28.
`
`Independent claim 18 of the ’431 patent is directed, generally speaking,
`
`to an
`
`aqueous liquid preparation consisting essentially of (a) bromfenac or a phannacologically
`
`acceptable salt or hydrate of bromfenac, where the hydrate is at least one selected from a 1/2
`
`hydrate,
`
`1 hydrate and 3/2 hydrate, (b) tyloxapol, (c) boric acid,
`
`((1) sodium tetraborate, (e)
`
`EDTA sodium salt, (0 benzalkonium chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite.
`
`The aqueous liquid preparation of claim 18 is formulated for ophthalmic administration, and
`
`benzalkonium chloride is the only quaternary ammonium compound included in the aqueous
`
`liquid preparation of claim 18.
`
`(’431 patent at col. 13, line 15 — col. 14, line 9.)
`
`29.
`
`Dependent claim 19 of the ’43l patent is directed, generally speaking, to the
`
`aqueous liquid preparation of claim 18, where (a) is a bromfenac sodium salt.
`
`(’431 patent at col.
`
`14, lines 10-12.)
`
`30.
`
`Dependent claim 20 of the ’431 patent is directed, generally speaking, to the
`
`aqueous liquid preparation of claim 19, where the concentration of bromfenac sodium salt is
`
`from about 0.01 to about 0.5% and the concentration of tyloxapol is about 0.02 w/v%.
`
`(’43l
`
`patent at col. 14, lines 13-16.)
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`2.
`
`The ’290 Patent Claims
`
`31.
`
`The claims of the ’290 patent are directed, generally speaking, to stable aqueous
`
`liquid preparations of bromfenac.
`
`(’290 patent at col. 12, line 1 - col. 15, line 8.)
`
`I understand
`
`that Defendants have raised claim construction disputes regarding certain claims of the ’290
`
`patent.
`
`I understand that Plaintiffs have asserted that Defendants have infringed claims 1-4 and
`
`6-30 of the ’29O patent.
`
`32.
`
`Independent claim 1 of the ’290 patent is directed, generally speaking, to a stable
`
`aqueous liquid preparation comprising two components, where the first component is bromfenac
`
`or a pharmacologically acceptable salt or hydrate of bromfenac, where the hydrate is at least one
`
`selected from a 1/2 hydrate,
`
`1 hydrate and 3/2 hydrate, where the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation, and where the second component
`
`is tyloxapol and is present in the liquid preparation in an amount sufficient to stabilize the first
`
`component. The stable aqueous liquid preparation of claim 1
`
`is fonnulated for ophthalmic
`
`administration. (’290 patent at col. 12, lines 2-12.)
`
`33.
`
`Dependent claim 2 of the ’290 patent
`
`is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, further comprising a quaternary ammonium salt.
`
`(’290
`
`patent at col. 12, lines 13-14.)
`
`34.
`
`Dependent claim 3 of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the first component is a bromfenac sodium salt.
`
`(’290 patent at col. 12, lines 15-17.)
`
`35.
`
`Dependent claim 4 of the ’290 patent
`
`is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the concentration of tyloxapol is from about 0.01
`
`w/v% to about 0.05 w/v %, where the first component is a bromfenac sodium salt, and where the
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`concentration of the bromfenac sodium salt is from about 0.01 to about 0.2 w/v%.
`
`(’290 patent
`
`at col. 12, lines 18-25.)
`
`36.
`
`Dependent claim 6 of the ’290 patent
`
`is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the pH is from about 7.5 to about 8.5. (’290 patent
`
`at col. 12, lines 29-30.)
`
`37.
`
`Dependent claim 7 of the ’290 patent is directed, generally speaking, to the stable
`
`aqueous liquid preparation of claim 1, where the stable aqueous liquid preparation consists
`
`essentially of (a) bromfenac sodium salt, (b) tyloxapol, (c) boric acid, ((1) sodium tetraborate, (e)
`
`EDTA sodium salt, (0 benzalkonium chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite.
`
`The stable aqueous liquid preparation of claim 7 is formulated for ophthalmic administration.
`
`The concentration of the bromfenac sodium salt in the stable aqueous liquid preparation of claim
`
`7 is from about 0.02 W/V °/o to about 0.1 w/v %. (’290 patent at col. 12, lines 31-40.)
`
`38.
`
`Independent claim 8 of the ’290 patent is directed, generally speaking, to a stable
`
`aqueous liquid preparation comprising two components, where the first component is bromfenac
`
`or a pharmacologically acceptable salt or hydrate of bromfenac, where the hydrate is at least one
`
`selected from a 1/2 hydrate,
`
`1 hydrate and 3/2 hydrate, where the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation, and where the second component
`
`is tyloxapol. The stable aqueous liquid preparation of claim 8 is formulated for ophthalmic
`
`administration and is characterized in that greater than about 90% of the original amount of the
`
`first component remains in the preparation after storage at about 60° C. for 4 weeks. (’290 patent
`
`at col. 12, lines 41-53.)
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`39.
`
`Dependent claim 9 of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 8, further comprising a quaternary ammonium salt.
`
`(’290
`
`patent at col. 12, lines 54-55.)
`
`40.
`
`Dependent claim 10 of the ’290 patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 8, where the stable aqueous liquid preparation is
`
`characterized in that greater than about 92% of the original amount of the first component
`
`remains in the preparation after storage at about 60° C. for 4 weeks.
`
`(’290 patent at col. 12, lines
`
`56-60.)
`
`41.
`
`Dependent claim 11 of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 8, where the concentration of tyloxapol is from about 0.01
`
`w/v % to about 0.05 w/V %, where the first component is a bromfenac sodium salt, and where the
`
`concentration of the bromfenac sodium salt is from about 0.01 to about 0.2 w/v%.
`
`(’290 patent
`
`at col. 12, lines 61-67.)
`
`42.
`
`Dependent claim 12 of the ’290 patent is directed, generally speaking, to the
`
`aqueous liquid preparation of claim 11, where the pH is from about 7.5 to about 8.5.
`
`(’290
`
`patent at col. 13, lines 1-2.)
`
`43.
`
`Dependent claim 13 of the ’290 patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 8, where the stable aqueous liquid preparation consists
`
`essentially of (a) bromfenac or a pharmacologically acceptable salt or hydrate of bromfenac,
`
`where the hydrate is at least one selected from a 1/2 hydrate,
`
`1 hydrate and 3/2 hydrate, (b)
`
`tyloxapol, (c) boric acid,
`
`((1) sodium tetraborate,
`
`(e) BDTA sodium salt,
`
`(1) benzalkonium
`
`chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite. The concentration of the bromfenac
`
`10
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`sodium salt in the stable aqueous liquid preparation of claim 13 is from about 0.02 w/v % to
`
`about 0.1 w/v %. (‘Z90 patent at col. 13, lines 3-13.)
`
`44.
`
`Independent claim 14 of the ’290 patent is directed, generally speaking, to a stable
`
`aqueous liquid preparation comprising two components, where the first component is bromfenac
`
`or a pharmacologically acceptable salt or hydrate of bromfenac, where the hydrate is at least one
`
`selected from a 1/2 hydrate, 1 hydrate and 3/2 hydrate, where the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation, and where the second component
`
`is tyloxapol. The stable aqueous liquid preparation of claim 14 is formulated for ophthalmic
`
`administration and does not include mannitol. (’290 patent at col. 13, lines 14-25.)
`
`45.
`
`Dependent claim 15 of the ’290 patent is directed, generally speaking, to the
`
`aqueous liquid preparation of claim 14, further comprising a quaternary ammonium salt.
`
`(’290
`
`patent at col. 13, lines 26-27.)
`
`46.
`
`Dependent claim 16 of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 14, where the first component is a bromfenac sodium salt.
`
`(’290 patent at col. 13, lines 28-30.)
`
`47.
`
`Dependent claim 17 of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 16, where the concentration of tyloxapol is from about 0.01
`
`w/v % to about 0.05 w/v % and the concentration of bromfenac sodium salt is from about 0.05 to
`
`about 0.2 w/v %.
`
`(’29O patent at col. 13, lines 31-35.)
`
`48.
`
`Dependent claim 18 of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 17, where the pH is from about 7.5 to about 8.5.
`
`(’290
`
`patent at col. 13, lines 36-37.)
`
`11
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`49.
`
`Dependent claim 19 of the ’290 patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 14, where the stable aqueous liquid preparation
`
`consists essentially of (a) bromfenac or a pharmacologically acceptable salt or hydrate of
`
`bromfenac, where the hydrate is at least one selected from a 1/2 hydrate,
`
`1 hydrate and 3/2
`
`hydrate,
`
`(b)
`
`tyloxapol,
`
`(c) boric acid, (d) sodium tetraborate, (e) EDTA sodium salt,
`
`(f)
`
`benzalkonium chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite. The concentration of
`
`the bromfenac sodium salt in the stable aqueous liquid preparation of claim 19 is from about 0.02
`
`w/v % to about 0.1 w/v %. (’290 patent at col. 13, lines 38-48.)
`
`50.
`
`Dependent claim 20 of the ’290 patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 14, where the stable aqueous liquid preparation is
`
`characterized in that greater than about 90% of the original amount of the first component
`
`remains in the preparation after storage at about 60° C. for 4 weeks. (’290 patent at col. 13, lines
`
`49-53.)
`
`51.
`
`Dependent claim 2] of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 20, further comprising a quaternary ammonium salt.
`
`(’290
`
`patent at col. 13, lines 54-55.)
`
`52.
`
`Dependent claim 22 of the ’290 patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 20, where the stable aqueous liquid preparation is
`
`characterized in that greater than about 92% of the original amount of the first component
`
`remains in the preparation afier storage at about 60° C. for 4 weeks. (’290 patent at col. 13, lines
`
`56-60.)
`
`53.
`
`Dependent claim 23 of the ’290 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 20, where the concentration of tyloxapol is from about 0.01
`
`12
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`w/v % to about 0.05 w/v %, where the first component is a bromfenac sodium salt, and where the
`
`concentration of the bromfenac sodium salt is from about 0.01 to about 0.2 w/v%.
`
`(’290 patent
`
`at col. 13, lines 61-67.)
`
`54.
`
`Dependent claim 24 of the ’290 patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 23, where the pH is from about 7.5 to about 8.5. (’290
`
`patent at col. 14, lines 1-2.)
`
`55.
`
`Dependent claim 25 of the ’290 patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 20, where the stable aqueous liquid preparation
`
`consists essentially of (a) bromfenac or a pharmacologically acceptable salt or hydrate of
`
`bromfenac, where the hydrate is at least one selected from a 1/2 hydrate,
`
`1 hydrate and 3/2
`
`hydrate, Go)
`
`tyloxapol,
`
`(c) boric acid,
`
`(d) sodium tetraborate,
`
`(e) EDTA sodium salt,
`
`(I)
`
`benzalkonium chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite. The stable aqueous
`
`liquid preparation of claim 25 is formulated for ophthalmic administration and the concentration
`
`of the bromfenac sodium salt in the stable aqueous liquid preparation of claim 25 is from about
`
`0.02 w/v % to about 0.1 w/v %. (’290 patent at col. 14, lines 3-14.)
`
`56.
`
`Dependent claims 26-30 of the ’290 patent are directed, generally speaking, to the
`
`aqueous liquid preparations of claims 1, 8, 14, 20, and 22, respectively, where the aqueous liquid
`
`preparation further satisfies the preservative efficacy standard of EP-criteria B of the European
`
`Pharmacopoeia as follows: viable cell counts of bacteria (S. aureus, P. aeruginosa) 24 hours and
`
`7 days after inoculation decrease to not more than 1/10 and not more than 1/1000, respectively,
`
`and thereafter, the cell count levels off or decreases; and viable cell count of fungi (C. albicans,
`
`A. niger) 14 days after inoculation decreases to not more than 1/10, and thereafter, the cell count
`
`13
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`keeps the same level as that of 14 days after inoculation.
`
`(’29O patent at col. 14, line 15 — col. 15,
`
`line 8.)
`
`3.
`
`The ’l3l Patent Claims
`
`57.
`
`The claims of the ’131 patent are directed, generally speaking, to stable aqueous
`
`liquid preparations of bromfenac.
`
`(’131 patent at col. 12, line 1 - col. 15, line 8.)
`
`I understand
`
`that Defendants have raised claim construction disputes regarding certain claims of the ’l31
`
`patent.
`
`I understand that Plaintiffs have asserted that Defendants have infringed claims 1-30 of
`
`the ’ 131 patent.
`
`58.
`
`Independent claim 1 of the ’l31 patent is directed, generally speaking, to a stable
`
`aqueous liquid preparation comprising two components, where the first component is bromfenac
`
`or a pharmacologically acceptable salt or hydrate of bromfenac, where the hydrate is at least one
`
`selected from a 1/2 hydrate,
`
`1 hydrate and 3/2 hydrate, where the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation and is present at a concentration
`
`from about 0.05 w/v % to about 0.2 w/v %, and where the second component is tyloxapol and is
`
`present in the liquid preparation in an amount sufficient to stabilize the first component. The
`
`stable aqueous liquid preparation of claim 1
`
`is formulated for ophthalmic administration. (’l3l
`
`patent at col. 12, lines 2-14.)
`
`59.
`
`Dependent claim 2 of the ’131 patent
`
`is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, further comprising a quaternary ammonium salt.
`
`(’l3l
`
`patent at col. 12, lines 15-16.)
`
`60.
`
`Dependent claim 3 of the ’l31 patent
`
`is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the first component is a bromfenac sodium salt.
`
`(’131 patent at col. 12, lines 18-20.)
`
`14
`
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`Case 1:14-cv-00667-JBS-KMW Document 80-6 Filed 08/10/15 Page 16 of 110 Page|D: 2697
`
`61.
`
`Dependent claim 4 of the ’131 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the concentration of tyloxapol is from about 0.01
`
`w/v% to about 0.05 w/v %. (’l31 patent at col. 12, lines 21-23.)
`
`62.
`
`Dependent claim 5 of the ’131 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 1, where the pH is from about 7.5 to about 8.5.
`
`(’131 patent
`
`at col. 12, lines 24-25.)
`
`63.
`
`Dependent claim 6 of the ’13l patent is directed, generally speaking, to the stable
`
`aqueous liquid preparation of claim 1, where the stable aqueous liquid preparation consists
`
`essentially of (a) bromfenac sodium salt, (b) tyloxapol, (c) boric acid, (d) sodium tetraborate, (e)
`
`EDTA sodium salt, (t) benzalkonium chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite.
`
`The stable aqueous liquid preparation of claim 6 is formulated for ophthalmic administration. In
`
`the stable aqueous liquid preparation of claim 6, the concentration of the bromfenac sodium salt
`
`is from about 0.02 w/v % to about 0.1 w/v %, and the concentration of tyloxapol is from about
`
`0.01 w/v % to about 0.05 w/v %. (’l31 patent at col. 12, lines 26-36.)
`
`64.
`
`Independent claim 7 of the ’131 patent is directed, generally speaking, to a stable
`
`aqueous liquid preparation comprising two components, where the first component is bromfenac
`
`or a pharmacologically acceptable salt or hydrate of bromfenac, where the hydrate is at least one
`
`selected from a 1/2 hydrate,
`
`l hydrate and 3/2 hydrate, where the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation and is present at a concentration
`
`from about 0.05 w/v °/o to about 0.2 w/v %, and where the second component is tyloxapol. The
`
`stable aqueous liquid preparation of claim 7 is formulated for ophthalmic administration and is
`
`characterized in that greater than about 90% of the original amount of the first component
`
`15
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`
`remains in the preparation after storage at about 60° C. for 4 weeks. (’l3l patent at col. 12, lines
`
`37-51.)
`
`65.
`
`Dependent claim 8 of the ’l31 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 7, further comprising a quaternary ammonium salt.
`
`(’l31
`
`patent at col. 12, lines 52-53.)
`
`66.
`
`Dependent claim 9 of the ’l3l patent is directed, generally speaking, to the stable
`
`aqueous
`
`liquid preparation of claim 7, where the stable aqueous liquid preparation is
`
`characterized in that greater than about 92% of the original amount of the first component
`
`remains in the preparation after storage at about 60° C. for 4 weeks.
`
`(’ 1 31 patent at col. 12, lines
`
`54-58.)
`
`67.
`
`Dependent claim 10 of the ’131 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 7, where the concentration of tyloxapol is from about 0.01
`
`w/v % to about 0.05 w/v %, where the first component is a bromfenac sodium salt, and where the
`
`concentration of the bromfenac sodium salt is from about 0.05 to about 0.1 w/v%. (’l3l patent
`
`at col. 12, lines 59-65.)
`
`68.
`
`Dependent claim 11 of the ’13l patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation of claim 10, where the pH is from about 7.5 to about 8.5.
`
`(‘I31
`
`patent at col. 12, lines 66-67.)
`
`69.
`
`Dependent claim 12 of the ’l3l patent is directed, generally speaking,
`
`to the
`
`stable aqueous liquid preparation of claim 7, where the stable aqueous liquid preparation consists
`
`essentially of (a) bromfenac or a phannacologically acceptable salt or hydrate of bromfenac,
`
`where the hydrate is at least one selected from a 1/2 hydrate,
`
`1 hydrate and 3/2 hydrate, (b)
`
`tyloxapol, (c) boric acid,
`
`((1) sodium tetraborate, (e) EDTA sodium salt, (0 benzalkonium
`
`16
`
`Page 17 of 110
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`
`chloride, (g) polyvinylpyrrolidone, and (h) sodium sulfite. The concentration of the bromfenac
`
`sodium salt in the stable aqueous liquid preparation of claim 12 is from about 0.05 w/v % to
`
`about 0.1 w/v % and the concentration of tyloxapol is about 0.02 w/v%.
`
`(’ 131 patent at col. 13,
`
`lines 1-12.)
`
`70.
`
`Independent claim 13 of the ’ 131 patent is directed, generally speaking, to a stable
`
`aqueous liquid preparation comprising two components, where the first component is bromfenac
`
`or a pharmacologically acceptable salt or hydrate of bromfenac, where the hydrate is at least one
`
`selected from a 1/2 hydrate,
`
`1 hydrate and 3/2 hydrate, where the first component is the sole
`
`pharmaceutical active ingredient contained in the preparation and is present at a concentration
`
`from about 0.05 w/v % to about 0.2 w/v %, and where the second component is tyloxapol. The
`
`stable aqueous liquid preparation of claim 13 is formulated for ophthalmic administration and
`
`does not include mannitol.
`
`(’131 patent at col. 13, lines 13-24.)
`
`71.
`
`Dependent claim 14 of the ’131 patent is directed, generally speaking,
`
`to the
`
`aqueous liquid preparation