Case513-cv-01927-LHK
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`Document88-1
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`FiIedO4/24/14
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`Pagel of 21
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`UNITED STATES DISTRICT COURT
`NORTHERN DISTRICT OF CALIFORNIA
`
`Case No 513-CV-1927 LHK PSG
`DECLARATION OF MICHAEL
`MAYERSOHN PH.D IN SUPPORT OF
`DEFENDANTS CLAIM
`CONSTRUCTION BRIEF
`
`Date
`Time
`Couifroom
`Judge
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`June 12 2014
`130 p.m
`84th Floor
`Hon Lucy
`
`Koh
`
`Case No 513-C V-2416 LHK PSG
`
`Case No 513-CV-2420 LHK PSG
`
`PAR PHARMACEUTICALS INC AND
`HANDA PHARMACEUTICALS LLC
`
`Plamtiffs
`
`TAKEDA PHARMACEUTICAL CO LTD
`TAKEDA PHARMACEUTICALS NORTH
`AMERICA INC TAKEDA
`PHARMACEUTICALS AMERICA INC
`AND TAKEDA PHARMACEUTICALS
`U.S.A INC
`
`Defendants
`TAKEDA PHARMACEUTICAL CO LTD.
`TAKEDA PHARMACEUTICALS U.S.A.
`INC AND TAKEDA
`PHARMACEUTICALS AMERICA INC
`
`Plaintiffs
`
`IMPAX LABORATORIES INC.
`
`Defendant
`_______________________________________
`TAKEDA PHARMACEUTICAL CO LTD.
`TAKEDA PHARMACEUTICALS U.S.A
`INC. AND TAKEDA
`PHARMACEUTICALS AMERICA INC
`
`Plaintiffs
`
`TWI PHARMACEUTICALS INC
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`Defendant
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`XHIBIT
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`JUI1262015
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`Daniefle Grant
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`Page 1 of 21
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`Patent Owner Ex. 2020
`Lupin v. Pozen
`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`Document88-1
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`FiIedO4/24/14
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`Page2 of 21
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`TABLE OF CONTENTS
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`Pages
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`QUALIFICATIONS
`BACKGROUND
`OPINIONS AND BASES THEREFORE
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`II
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`ifi
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`Person of Ordinary Skill
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`in the Art
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`Construction of Disputed Claim Terms of the 158 Patent
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`regardless of whether the patient is imder fasted or fed conditions
`claim
`enteric coating releases the proton pump inhibitor from the solid
`pH of about 5.0 to about 5.5
`about 6.2 to about 6.8
`particle at
`claiml
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`enteric coating has
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`pH of about 5.5 or about 6.75 claims
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`and
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`wherein the changes in phannacolcinetics.
`under fasting or fed
`conditions does not prodnce statistically significant changes in
`intragastric PH claim
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`Patent Owner Ex. 2020
`Lupin v. Pozen
`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`Document8B-1
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`FiIedO4/24/14
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`Page3 of 21
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`Michael Mayersohn Ph.D declare as follows
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`submit this declaration in support of the claim construction brief submitted by
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`defendants Impax Laboratories Inc Par Pharmaceutical
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`Inc Handa Pharmaceuticals LLC and T\Vi
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`Pharmaceuticals Inc collectively Defendants
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`In particular
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`submit this declaration to provide relevant background information
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`regarding the technology at issue in U.S Patent No 8173158 the 158 patent and to set forth my
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`opinions regarding the meaning of the disputed claim terms from the perspective of person of
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`ordinary skill
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`in the pertinent art at the relevant time
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`QIh%JAFICATIONS
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`The following is
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`brief summary of my qualifications My qualifications are more
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`fully set forth in my curriculum vitae attached as Exhibit
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`was awarded the degree of Bachelor of Science in Phannacy in 1966 from Columbia
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`University College of Phannaceutical
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`Sciences and Ph.D in Pharmaceutics
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`from the School of
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`Pharmacy State University of New York at Buffalo in 1971
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`was licensed by the State of New York to practice phannacy in 1967 and practiced
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`pharmacy in Buffalo New York from that time until 1971
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`Following receipt of my doctoral degree
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`became an Assistant Professor in the Faculty
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`of Pharmacy at
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`the University of Toronto in Canada and became an Associate Professor there in 1975
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`have been
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`faculty member of the College of Pharmacy at the University of Arizona
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`in Tucson since 1976 starting as an Associate Professor
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`have been
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`full Professor since 1983
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`copy of the 158 patent
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`is attached as Exhibit
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`Patent Owner Ex. 2020
`Lupin v. Pozen
`IPR2015-01775
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`

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`Case513-cv--01927-LHK
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`Document88-1
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`have been member of the Interdisciplinary Graduate Program in Phannacology and
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`Toxicolo2y the Center for Toxicology and the Southwest Environmental Health Sciences Center all
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`of which are at the University of Arizona
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`My research interests include the general area of pharmaceutical sciences with
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`specialty in pharmaceutics biopharmaceutics and pharmacokinetics
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`including
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`the examination of
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`the relationship between the physical and chemical characteristics of
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`drug and its dosage form and
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`the fate and perfonnance of that drug in the body and
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`the development of rigorous mathematical
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`models to quantitate the kinetic processes of drug absorption distribution excretion metabolism and
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`clmical or pham1acologlcal response
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`have maintained an active research program which has been fbnded by national state
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`and private agencies- This program has involved numerous research projects and the supervision of
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`many graduate students post-doctoral
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`fellows and technicians
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`have conducted research studies in vitro to characterize the physical and chemical
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`properties of drugs and drug dosage forms including dissolution rates stability and binding to other
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`compounds These studies have included an examination of the properties of variety of drug dosage
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`forms including innnediate and non-innnediate release oral formulations
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`have also conducted in vitro and in vivo studies to characterize the plasma protein
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`binding of drugs and their metabolic properties in the presence of varying enzymatic preparations
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`have conducted in sit and whole animal studies in mice rats dogs and pigs to
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`characterize the pharmacokinetics and phannacodynamics of drugs and their metabolites
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`have conducted clinical studies in human subjects to evaluate the phaunacokinetics of
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`selected drugs and their metabolites
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`In all of the above studies
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`developed selective sensitive and
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`reliable quantitative analytical methods
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`Patent Owner Ex. 2020
`Lupin v. Pozen
`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`In addition have performed theoretical or in silico experiments using simulation
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`and other mathematical/computer
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`techniques in order to answer specific questions concerning the
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`disposition or interaction of drugs
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`am member of several professional societies and organizations including the
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`American Association of Phannaceutical Scientists the American Society for Clinical Pharmacology
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`and Therapeutics and the American Society of Pharmacology and Experimental Therapeutics
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`have reviewed and continue to review publications for several peer-reviewed journals
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`including the Journal of Pharmaceutical Sciences and Pharmaceutical Research
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`have been member of ninnerous national and state grant review agencies National
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`Institutes of Health Veterans Administration etc for which
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`reviewed research grant applications
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`have published over 160 original research publications 18 book chapters and
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`symposia and 15 professional/educational pubhcations
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`have given more than 65 invited
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`presentations and contributed to over 160 submitted presentations
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`During the years 1995-1998
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`was member of the Food and Drug Administration
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`Committee This Connnittee advises the FDA in setting standards for bioavailability bioequivalence
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`Sciences fonnerly the Generic Drug Advisory
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`and in resolving mailers of scientific interest to the agency
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`served one five-year
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`term as member of the Dissolution and Bioavailability Expert
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`Conmiittee of the United States Pharmacopoeia
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`and
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`subsequent
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`five-year term as Vice Chair of the
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`same Conmiittee whose name was changed to the Biopharmaceutics Expert Committee This
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`Committee sets standards for dissolution testing and for drugs that are incorporated into individual
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`monographs
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`am also the Course Director and Instructor of Principles of Pharmacokinetics and
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`Toxicokinetics for the Industrial Scientist which is sponsored by the University of Arizona and given
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`Case513-cv-01927-LHK
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`to pharmaceutical scientists This course has been successfluly offered since 1994 and has em-oiled
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`well over 600 scientists
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`ani also Course Director of similar on-site courses offered to the
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`pharmaceutical
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`industry and which have enrolled well over 1000 scientists
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`lam being compensated for my work in this case at my standard rate of $800 per hour
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`My compensation is not affected by the outcome of this matter
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`II
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`BACKGROUND
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`24
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`The 158 patent generally relates to methods of treating heartburn acid reflux or
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`gastroesophageal
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`reflux disease by administering
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`pharmaceutical composition containing small
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`organic molecules called proton pump inhibitors PPIs In particular the 158 patent relates to
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`the use of pharmaceutical composition comprising
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`specific PPI called dexlansoprazole
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`PPIs help
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`to treat these conditions by shntting down proton pumps in the stomach that produce acid thereby
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`reducmg the amount of acid in the stomach
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`PPIs usually are administered orally in the form of
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`tablet or
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`capsule containing
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`granules that encapsulate the PPI Because PPIs are chemically imstable in the acidic environment of
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`the stomach they must be protected from stomach acid Drug manufacturers accomplish this by
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`combining the PPI with various stabilizers and coatings resulting in drug formulation that has an
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`outer layer referred to as the enteric coat that protects the PPI from stomach acid
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`The enteric
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`coat allows the drug to pass through the stomach intact ending up in the small intestine where the PPI
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`can be released and absorbed by the body
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`The reason the enteric-coated drug formulation can pass through the stomach and
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`protect
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`the PPI from acid-degradation is because the enteric coat is sensitive to the pH of its
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`environment This pH-sensitivity allows the enteric coat to remain intact or undissolved in the highly
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`________________________
`typical representation of such
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`declaration
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`layered formulation is shown in paragraph 53 of the Sinko
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`IPR2015-01775
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`Case513-cv-01927-LHK
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`Document88-1
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`F11ed04124114
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`acidic environment of the stomach bitt permits the coating to dissolve in the less acidic enviromnent
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`of the small intestine thereby allowing the encapsulated PPI
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`to be released from the drug formnlation
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`in the small intestine where it can then be absorbed
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`Varions PPIs are currently available on the market with number available in both
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`branded and generic formulations The first PPI that became conimercially available omeprazole was
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`sold imder the brand name Prilosec and has been on the market since 1989 Other PPIs such as
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`lansoprazole which is sold under the brand name Prevacid and esomeprazole
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`single enantiomeric
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`form of the raceinic drug omeprazole sold imder the brand name Nexium subsequently became
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`available Prevacid generically knovn as lansoprazole is sold by Takeda and lost its patent
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`protection in 2009 Dexilant
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`the drug at issue in this case is
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`variant i.e.
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`single enantiomer of
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`lansoprazole and another member of the closely related PPI family of drugs Dexilant became
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`commercially available in 2009 the same year Takeda lost its patent protection on its Prevacid drug
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`product
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`The pharmaceutical composition disclosed in the 158 patent
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`is made up of two types of
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`enteric-coated particles comprising the PPI dexlansoprazole 158 Pat Claim
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`The first particle
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`has an enteric coating that must release the PPI at
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`pH of about 5.0 to about 5.5 Id The second
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`particle has an enteric coating that must release the PPI at pH of about 6.2 to about 6.8 Id
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`Moreover the formulation must be therapeutically effective whether the dosage form is administered
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`to
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`patient who is on an empty stomach that
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`is imder fasting conditions or has eaten at various
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`times that
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`is under fed conditions Id
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`The 158 patent discloses three strengths of the phannaceutical composition 30 mg 60
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`and the use of one of those strengths the 90 mg in Example
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`to describe the compositions for each of these pharmaceutical
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`fonnulations
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`Tables
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`and
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`piuport
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`formulations Rather Table
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`lists
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`range of percentages of polymers that may be used in the enteric coatings of the granules and Table
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`lists ranges of the various excipients without even naming what the actual excipients should be For
`dose in granule LL can
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`example Table
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`states that
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`the proportion of TAK-390
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`be 15%_500o and in granule
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`can be between 500 o-85% of the total dose Similarly Table
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`lists
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`ranges for the ingredients in
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`composition for Granules-LL and Table
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`lists ranges for the
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`ingredients in composition for Granules-H The ranges for these ingredients are quite broad and
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`the actual
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`ingredient
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`is not identified specifically but only by fimction For example the amotmt of
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`diluent can be behveen 5.0 and 30.0 percent and no specific diluent
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`is listed Thus Example
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`discloses various ranges for the types of ingredients used in the formulations resulting in numerous
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`possible compositions for each formulation such that
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`the exact composition of the fonnulation used in
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`Example
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`cannot be ascertained from the information provided
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`The 158 patent
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`includes an example Example
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`that discloses clinical studies
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`performed on patients using the 90 mg strength of the pharmaceutical composition that includes these
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`two types of enteric-coated particles comprising dexlansoprazole 158 Pat at 2336-2717 In
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`particular the pharmaceutical composition was administered to healthy adult subjects under fasting
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`conditions after an overnitht fast as well as under three fed conditions
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`minutes before dosing 30
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`minutes before dosing and 30 minutes after dosing 158 Pat at 241-6 Table
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`Both the plasma
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`concentrations
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`of dexlausoprazole as
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`fimction of time as well as the pHs of the stomach fluids of the
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`subjects were recorded fri
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`at 2411-45 Tables 5-7 Based on these collected data various
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`pharmacolcinetics and pharmacodynamics parameters were then calculated and mathematically
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`analyzed to determine the effect of food and the timing of food on the therapeutic
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`effectiveness of the
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`phannaceutical
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`fonnulation Id
`Pharmacokinetics sometimes abbreviated as PK is
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`pharmaceutical science that
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`deals with the detennination of absorption distribution metabolism and excretion of drugs
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`IPR2015-01775
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`Case513-cv-01927-LHK
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`achninistered to the body It
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`is often described as examining the effect of the body on the drug This
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`is in contrast
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`to phannacology which is
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`qualitative examination of the effect of the drug on the
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`more quantitative imderstanding of the relationship between phannacokinetics and
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`body
`pharmacology is referred to as phannacodynamics sometimes abbreviated as PD in which one
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`examines the time-course of the effect of the drug on the body i.e the phannacological or clinical
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`response by quantitatively studying the time-course of the response and its relationship with the
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`plasma concentration-time profile
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`These two areas of study PK and PD are inextricably coimected The
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`phannacodynamic properties of drug are often studied in combination with its pharmacokinetic
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`properties to develop so-called pharmacokinetic/pharmacodynamic PlC/PD models of the drug in
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`individuals and populations of patients The pharmacokinetic and phannacodynamic events overlap
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`The driving force for the pharmacodynamic events following drug dosing is generally the
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`concentration of drug in the blood or plasma or the i-ate at which those concentrations
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`change It
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`is
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`for this reason that there is interest in being able to describe the plasma concentration-tine profile of
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`drug following its administration to
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`patient
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`Following the administration of drug for example after oral ingestion frequent blood
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`samples are obtained for
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`time sufficient
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`to characterize the entire plasma concentration-time profile
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`The blood samples or
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`fluid derived from blood e.g plasma or serum are treated aud subjected to an
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`analytical procedure from which one can obtain
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`quantitative vahie for the concentration of the drug
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`andlor metabolites of that drug in the blood fluid The resulting concentration-time profiles are then
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`analyzed either using
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`computer-based method to obtain mathematical model that best describes the
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`data or by model-independent method In either approach estimates of the values of the
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`phannacokinetic parameters of interest are obtained
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`Case513-cv-01927-LHK
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`PagelO of 21
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`stylized single-dose plasma concentration-time profile resulting from oral dosing is
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`depicted below As shown in the figure the maximum concentration
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`achieved is at the peak of
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`the curve and the time corresponding to that maximum is referred to as Tmn Also shown in the figure
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`is the total area mider the curve AUC which is related to the extent of absorption or total exposure to
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`the drug The latter value is measure related to the amount of drug that gets absorbed into the
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`patients blood
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`Cmax
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`AUC
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`Tmax
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`Time
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`35
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`The pharmacokinetic parameters
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`and AUC are reported in Example
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`of the
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`158 patent
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`for the fasted state as well as for the three fed states noted above 158 Pat at 2411-28
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`2462-2512 and Tables
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`and
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`These parameters are then analyzed and compared to determine
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`whether there are statistically significant differences between these parameters in the fasted and
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`various fed states KId In addition the 158 patent discloses the calculation of tsvo phannacodynamic
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`parameters to determine the effect of food mean intragastric pH and
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`time pH4 over 24 hours
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`post dose Id at 2434-38 2513-27 and Table
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`The mean intragastric pH parameter refers to
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`the statistical mean determined from the pH measurement data The
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`time parameter refers to the
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`percentage of time that
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`the pH of the stomach fluid is eater than pH
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`over
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`period of 24 hours after
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`the patient is dosed
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`Patent Owner Ex. 2020
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`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`Document88-1
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`FiIedO4/24/14 Pagell of 21
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`III
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`OPINIONS AND BASES THEREFORE
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`Person of Ordinary Skill
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`in the Art
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`36
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`For purposes of my analysis have considered how the tenns of the 158 patent would
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`have been understood from the viewpoint of person of ordinary skill
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`in the art
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`In my opinion the art
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`relevant to the claimed subject mailer is pharmaceutical drug development and analysis in particular
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`clinical pharmacokinetics and clinical phannacodynamics
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`person of ordinary skill
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`in the art would
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`have had
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`high level of education and skill
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`including an M.D Ph.D or Pharm.D in
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`phannaceutical sciences medicine or
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`related field and two years of work experience in the
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`appropriate field or alternatively Bachelors or Masters Degree and
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`commensurately greater
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`number of years of experience in the appropriate field
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`have been asked by counsel
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`to read the claim tenns from the perspective of
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`person
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`of ordinary skill
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`in the art in October 2007 which mderstand is the date on which the earliest
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`application that
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`led to the 158 patent was filed As of October 2007 and at all
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`times since would
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`have qualified as
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`person of at least ordinary skill
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`in the art
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`Construction of Disputed Claim Terms of the 158 Patent
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`38
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`understand that Takeda has asserted claims 1-8 of the 158 patent against
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`the
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`Defendants
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`in this case Claims
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`and
`
`are representative and read as follows
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`method of treating heartburn acid refiux or gastroesophageal
`the method
`patient in need of treatment thereof
`refiux disease in
`comprising the steps of
`obtaining
`pharmaceutical composition
`comprising dexlansoprazole from group of pharmaceutical
`compositions comprising proton pump inhibitors and
`administering
`patient suffering from heartburn acid refiux or gastroesophageal
`to
`the patient is under fasted or fed
`reflux regardless of whether
`therapeutically effective amoimt of the pharmaceutical
`conditions
`composition obtained in step
`wherein the pharmaceutical composition
`first solid particle wherein said first solid particle
`comprises
`comprises dexlansoprazole and
`first enteric coating wherein the first
`enteric coating releases the proton pump inhibitor from the solid
`pH of about 5.0 to about 5.5 and ii
`second solid
`particle at
`particle wherein said second solid particle comprises dexlansoprazole
`second enteric coating wherem the second enteric coating
`and
`pH of
`releases the proton pump inhibitor from the solid particle at
`about 6.2 to about 6.8 wherein the first solid particle comprises from
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`Page 11 of 21
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`Lupin v. Pozen
`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`Document88-1
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`FiIedO4/24/14
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`Pagel2 of 21
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`S0o to about 50 by weight of the phannaceutical composition
`about
`and the second solid particle comprises from about 50% to about 85% by
`weight of the pharmaceutical composition
`
`The method of claim wherein the first enteric coating has
`about 5.5
`
`pH of
`
`The method of claim wherein the second enteric coating has
`of about 6.75
`
`pH
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`The method of claim wherein the changes in pharmacokinetics
`after administration to the patient of
`single dose of
`therapeutically
`effective amomt of the pharmaceutical composition comprising
`dexlansoprazole under fasting or fed conditions does not produce
`statistically significant changes in intragastric pH
`
`158 patent
`
`Claims 1-4 disputed phrases bolded
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`regardless of whether
`
`the patient is under fasted or fed conditions claim
`
`Defendants Construction
`
`Regardless of whether the patient is dosed
`after an overnight fast within minutes
`before meal within 30 minutes before
`meal or within 30 minutes after meal
`
`Takedas Construction
`regard to food
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`\\Tithout
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`39
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`understand that Defendants originally proposed
`
`construction that defined fasted or
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`fed conditions with respect
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`to whether and when
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`patient has eaten meal whereas the same
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`therapeutic
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`effect
`
`is achieved whether the patient has eaten meal will eat meal or is on an empty
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`stomach In my opinion Defendants original proposed defmition was consistent with the
`
`specification of the 158 patent which includes experimental results for several
`
`fasted and fed
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`conditions which vary depending on whether and when the patient has consumed
`
`high-fat breakfast
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`158 Pat at 2336-2717 Specifically the 158 patent
`
`includes results for testing conducted on
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`patients dosed under fasting conditions dosed 30 mm after the start of high-fat breakfast dosed
`
`mm before
`
`high-fat breakfast and dosed 30 mm before
`
`high-fat breakfast
`
`Id at Table
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`Defendants original proposed defmition covered these various fasted and fed conditions and further
`
`required that the administration of the phannaceutical dosage form under
`
`these conditions should
`
`result in the same therapeutic effect
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`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`Document88-1
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`FitedO4/24/14
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`Pagel3 of 21
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`40
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`also nnderstand that in an effort to construe claim terms appearing in different claims
`
`in the same way Defendants have generally agreed to adopt Takedas proposed construction for
`
`fasting or fed conditions in connection with its construction of that term in claim of the 158
`
`patent While Takeda has proposed to define fasted or fed conditions in claim to mean without
`
`regard to food Takeda has defined
`
`nearly identical
`
`term fasting or fed conditions
`
`entirely
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`differently in claim
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`Compare Takeda Br at 14 wit/i Takeda Br at 23 Specifically in connection
`
`with claim Takeda defmes fasting conditions to mean dosing after an overnight fast and fed
`
`conditions to mean dosing within 30 minutes before or after meal id at 23 with the latter
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`covering two of the three fed conditions disclosed in the 158 specification
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`KId at 24 Bitt the only
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`difference between the fast/fed terms appearing in claims
`
`and
`
`is the replacement of fasted with
`
`fasting in claim There is no reason why they shonld be different
`
`the 158 patent
`
`treats these
`
`terms as identical and persons of ordinary skill
`
`in the art would have understood them to be identical
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`as well 158 Pat at Fig
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`Fig 2.41-4 2463-2565 Accordingly the construction for fasted or
`
`fed conditions in claim should be the same as that for fasting or fed conditions in claim
`
`41
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`also understand that Defendants have slightly modified Takeda
`
`construction for
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`fasting or fed conditions to recite each of the three fed conditions disclosed in the 158
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`specification rather than lumping them together as in Takeda
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`proposal Separately reciting each
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`condition is appropriate in the context of claim
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`because the plain meaning of claim requires
`
`therapeutically effective amount of the PPI to be administered irrespective of whether the patient has
`
`been dosed imder any of the fasted or fed conditions Exhibit
`
`defmes regardless as without
`
`tegaid to inespective of In other words the regardless term in claim requires
`
`therapeutic
`
`effect
`
`to be achieved no matter which state the patient
`
`is in 30 minutes after eating minutes before
`
`eating or 30 minutes before eating 158 Pat at Table
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`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`Document88-1
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`FiIedO4/24/14
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`Pagel4 of 21
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`42
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`Consistent with this requirement Defendants proposed defmition separately identifies
`
`the fasted state the fed state after the start of meal and the two fed states before the stall of meal
`
`to indicate that the therapeutic
`
`results must be achieved no matter which of these states the patient is in
`
`when dosed with the drug This construction is consistent with the specification which defmes
`
`fasted to mean after an ovemiaht
`
`fast 158 Pat at 23 63-244 and further defmes three fed
`
`conditions
`
`patient is dosed within 30 minutes after meal within minutes before meal or within
`
`30 minutes before meal 158 Pat at Table
`
`This construction is also consistent with the patents
`
`statements distinguishing the invention from previously-available PPIs which according to the patent
`
`should be taken shortly before eating meal 158 Pat at 24-15 966-1034
`
`enteric coating releases the proton pump inhibitor from the solid particle
`pH of about 5.0 to about 5.5 or about 6.2 to about 6.8 claim
`at
`
`Defendants Construction
`
`Enteric coating releases all of the proton
`pH
`pump inhibitor from the solid particle at
`pH of no more than
`of
`less than 4.95 to
`5.55f less than 6.15 to
`pH of no more
`than 6.85
`
`Takedas Construction
`The target pH for dissolution of the enteric
`coating is approximately 5.0 to
`
`approximately 5.5 or approximately 6.2 to
`approximately 6.8
`
`43
`
`Defendants proposed construction has two parts
`
`the enteric coating must release
`
`all of the proton inhibitor and
`
`the pH at which the release takes place must be about 5.0 to about
`
`5.5 or about 6.2 to about 6.8 where about is defmed to mean 0.05 pH units Once this defmition
`
`of about is applied to the pH levels recited in the claims the pH ranges become no less than 4.95 to
`
`no more than 5.55 and no less than 6.15 to no more than 6.85 In my opinion Defendants
`
`proposed construction is consistent with the intrinsic and extrinsic evidence
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`IPR2015-01775
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`

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`Case513-cv-01927-LHK
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`Document88-1
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`FiledO4/24/14
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`Pagel5 of 21
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`enteric coating releases the proton pump inhibitor at3
`
`pH of
`
`44
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`Defendants proposed construction requires that
`
`the enteric coating surrounding the PPI
`
`actually releases its PPI at or above
`
`particular pH This construction is consistent with the intrinsic
`
`evidence in particular the claim language which requires release of the PPI enteric coating releases
`
`the proton pump inhibitor
`
`at
`
`pH of
`
`158 Pat at Claim
`
`Defendants construction is also
`
`consistent with the specification wherein the first enteric coating releases the active agent
`
`from the
`
`solid particle at
`
`pH of about 5.0 to about 5.5 and wherein the second enteric coating releases the
`
`active agent
`
`from the solid particle at
`
`pH of about 6.2 to about 6.8
`
`second enteric coating
`
`surrounds the core and releases the active agent from the solid particle at
`
`pH of about 6.2 to about
`
`6.8 158 Pat at 236-45 1224-36 emphases added
`
`45
`
`In contrast Takeda
`
`proposed construction reads the release requirement entirely out
`
`of the claims while at the same time reading into the claims
`
`new requirement target pH for
`
`dissolution Instead of requiring as the claim recites that the PPI be released from the enteric
`
`coating at or above
`
`particular pH Takedas construction only looks to see what the enteric coat
`
`is
`
`made of
`
`If the enteric coat is made of material
`
`that
`
`is designed to dissolve at
`
`pH that corresponds
`
`to the claimed threshold pHs then under Takeda
`
`construction the formulation falls within the scope
`
`of the claims But enteric coats do not necessarily dissolve at the exact
`
`target pH at which they are
`
`supposed to dissolve Rather as discussed in detail
`
`in Dr Sinkos declaration the release of PPIs is
`
`affected by many more factors in addition to the pH such as thickness and uniformity of the enteric
`
`coating the nature of other excipients in the enteric coat and the testing conditions Thus Takeda
`
`proposed construction entirely eliminates the release requirement
`
`from the claims
`
`_________________________
`agree that the entirety of release need not occur at
`particular pH Defendants proposed
`particular pH which as Takedas expert Dr
`release at or above
`construction was intended to cover
`Sinko also agrees is the correct phraseology Sinko Decl 11 50 108 119 Thus the phrase at
`pH of
`pH of as used in Defendants proposed construction should be read to mean at or above
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`Patent Owner Ex. 2020
`Lupin v. Pozen
`IPR2015-01775
`
`

`
`Case513-cv-01927-LHK
`
`Document88-1
`
`FiIedO4/24/14
`
`Pagel6 of 21
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`46
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`Defendants construction also requires the release of all of the PPJ contained within the
`
`enteric coating after the claimed threshold pH is reached as modified by the word about Thus
`
`imder Defendants proposed construction the PPI must not begin to release below the recited threshold
`
`pHs Accordingly for the first pH term the release must begin at
`
`pH of no less than about SM and
`
`continue until completed and for the second pH term the release must begin at
`
`pH of no less than
`
`about 6.2 and continue until completed
`
`47
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`Without such
`
`requirement
`
`the bottom-end pH values recited in the claims become
`
`meaningless As discussed above the release of PPIs is affected by many more factors in addition to
`
`the pH such as thickness and uniformity of the enteric coating the nature of other excipients in the
`
`enteric coat and the testing conditions Thus unless the claimed pH-dependent
`
`release is limited to
`
`require that the release begin only after the claimed threshold pH is reached release at anvpH would
`
`fall within the scope of the claims if
`
`the other conditions are carefully manipulated For example the
`
`test conditions may be set in such way that release occurs substantially below the claimed threshold
`
`pH rendering the pH limitation meaningless
`
`48
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`Moreover whether release below the target pH is covered by the claims is not
`
`relevant here as the pH values in the claims are not the target pHs as discussed above The claims
`
`merely require that the drug begin releasing once
`
`particular pH value is reached Because the claims
`
`are not directed to the target pH it
`
`is not necessary to futher require that the claims cover
`
`release
`
`below the target pH To the extent any release below the recited pH ranges is covered by the claims it
`
`is that which is included in the expansion of the rang