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`UNITED STATES DISTRICT COURT
`NORTHERN DISTRICT OF CALIFORNIA
`
`Case No. 5:13-CV-1927 LHK (PSG)
`
`DECLARATION OF MICHAEL
`MA YERSOHN, PH.D. IN SUPPORT OF
`DEFENDANTS'CLAIM
`CONSTRUCTION BRIEF
`
`Date:
`Time:
`Courtroom:
`Judge:
`
`June 12, 2014
`1:30 p.m.
`8, 4th Floor
`Hon. Lucy H. Koh
`
`Case No. 5:13-CV-2416 LHK (PSG)
`
`Case No. 5:13-CV-2420 LHK (PSG)
`
`PAR PHARMACEUTICALS, INC. AND
`RANDA PHARMACEUTICALS, LLC,
`
`Plaintiffs,
`
`V.
`
`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,
`
`V.
`
`IMPAX LABORATORIES, INC.,
`
`Defendant.
`
`TAKEDA PHARMACEUTICAL CO., LTD.,
`TAKEDA PHARMACEUTICALS U.S.A.,
`INC., AND TAKEDA
`PHARMACEUTICALS AMERICA, INC.,
`
`Plaintiffs,
`
`V.
`
`TWI PHARMACEUTICALS, INC.,
`
`Defendant.
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`PTX-434.0001
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`Patent Owners' Ex. 2023
`IPR2018-00272
`Page 1 of 21
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`Case5:13-cv-01927-LHK Document88-1 Filed04/24/14 Page2 of 21
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`TABLE OF CONTENTS
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`2.
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`Page(s)
`QUALIFICATIONS ................................................................................................................. 1
`BACKGROUND ....................................... ........ .. ...... .......... .. ...... ........ .. ...... ....... ....... ........ .. .... 4
`OPINIONS AND BASES THEREFORE ................................................................................. 9
`A
`Person of Ordinary Skill in the Art ............................................................................... 9
`B.
`Construction of Disputed Claim Terms of the '158 Patent ........................................... 9
`1.
`"regardless of whether the patient is under fasted or fed conditions"
`(claim 1) .......................................................................................................... 10
`"enteric coating releases the proton pump inhibitor from the solid
`particle at a pH of' "about 5.0 to about 5.5" or "about 6.2 to about 6.8"
`(claim 1) .......................................................................................................... 12
`"enteric coating has a pH of' "about 5.5" or "about 6.75" (claims 2 and
`3) ..................................................................................................................... 15
`"wherein the changes in pharmacokinetics ... under fasting or fed
`conditions does not produce statistically significant changes in
`intragastric pH" (claim 4) ................................................................................ 17
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`3.
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`4.
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`I.
`11.
`III.
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`1
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`I, Michael Mayersohn, Ph.D., declare as follows:
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`1.
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`I submit this declaration in support of the claim construction brief submitted by
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`defendants Impax Laboratories, Inc., Par Pharmaceutical, Inc., Randa Pharmaceuticals LLC, and TWi
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`Pharmaceuticals, Inc. ( collectively, "Defendants").
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`2.
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`In particular, I submit this declaration to provide relevant background information
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`regarding the technology at issue in U.S. Patent No. 8,173,158 (the"' 158 patent"), 1 and to set forth my
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`opinions regarding the meaning of the disputed claim terms from the perspective of a person of
`
`ordinary skill in the pertinent art at the relevant time.
`
`I.
`
`QUALIFICATIONS
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`3.
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`The following is a brief summary of my qualifications. My qualifications are more
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`fully set forth in my curriculum vitae, attached as Exhibit B.
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`4.
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`I was awarded the degree of Bachelor of Science in Pharmacy in 1966 from Columbia
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`University College of Pharmaceutical Sciences and a Ph.D. in Pharmaceutics from the School of
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`Pharmacy, State University of New York at Buffalo in 1971.
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`5.
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`I was licensed by the State of New York to practice pharmacy in 1967 and practiced
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`pharmacy in Buffalo, New York from that time until 1971.
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`6.
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`Following receipt of my doctoral degree, I became an Assistant Professor in the Faculty
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`of Pharmacy at the University of Toronto in Canada and became an Associate Professor there in 1975.
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`7.
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`I have been a 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. I have been a full Professor since 1983.
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`1 A copy of the' 158 patent is attached as Exhibit A
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`8.
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`I have been a member of the Interdisciplinary Graduate Program in Pharmacology and
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`Toxicology, 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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`9.
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`My research interests include the general area of pharmaceutical sciences with a
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`specialty in pharmaceutics, biopharmaceutics and pharmacokinetics, including (a) the examination of
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`the relationship between the physical and chemical characteristics of a drug and its dosage form and
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`the fate and performance of that drug in the body, and (b) 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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`clinical or pharmacological response.
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`10.
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`I have maintained an active research program, which has been funded 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 fellows and technicians.
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`11.
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`I 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 a variety of drug dosage
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`forms, including immediate and non-immediate release oral formulations.
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`12.
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`I 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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`13.
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`I have conducted in situ and whole animal studies (in mice, rats, dogs and pigs) to
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`characterize the pharmacokinetics and pharmacodynamics of drugs and their metabolites.
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`14.
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`I have conducted clinical studies in human subjects to evaluate the pharmacokinetics of
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`selected drugs and their metabolites. In all of the above studies, I developed selective, sensitive and
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`reliable quantitative analytical methods.
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`15.
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`In addition, I have performed "theoretical" or in silica experiments using simulation
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`and other mathematical/computer techniques in order to answer specific questions concerning the
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`disposition or interaction of drugs.
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`16.
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`I am a member of several professional societies and organizations, including the
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`American Association of Pharmaceutical 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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`17.
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`I 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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`18.
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`I have been a member of numerous national and state grant review agencies (National
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`Institutes of Health, Veterans Administration, etc.) for which I reviewed research grant applications.
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`19.
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`I have published over 160 original research publications, 18 book chapters and
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`symposia, and 15 professional/educational publications. I have given more than 65 invited
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`presentations and contributed to over 160 submitted presentations.
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`20.
`
`During the years 1995-1998, I was a member of the Food and Drug Administration
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`("FDA") Advisory Committee for Pharmaceutical Sciences (formerly, the Generic Drug Advisory
`
`Committee). This Committee advises the FDA in setting standards for bioavailability, bioequivalence,
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`and in resolving matters of scientific interest to the agency.
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`21.
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`I served one five-year term as a member of the Dissolution and Bioavailability Expert
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`Committee of the United States Pharmacopoeia and a subsequent five-year term as Vice Chair of the
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`same Committee, 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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`22.
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`I 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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`PTX-434.0005
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`to pharmaceutical scientists. This course has been successfully offered since 1994 and has enrolled
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`well over 600 scientists. I am also a Course Director of similar on-site courses offered to the
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`pharmaceutical industry and which have enrolled well over 1000 scientists.
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`23.
`
`I am 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.
`
`II.
`
`BACKGROUND
`
`24.
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`The '158 patent generally relates to methods of treating heartburn, acid reflux, or
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`gastroesophageal reflux disease by administering a 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 a pharmaceutical composition comprising a specific PPI called dexlansoprazole. PPis help
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`to treat these conditions by shutting down proton pumps in the stomach that produce acid, thereby
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`reducing the amount of acid in the stomach.
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`25.
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`PPis usually are administered orally, in the form of a tablet or a capsule containing
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`granules that encapsulate the PPI. Because PPis are chemically unstable 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 a drug formulation that has an
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`outer layer (referred to as the "enteric coat") that protects the PPI from stomach acid. 2 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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`26.
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`The reason the enteric-coated drug formulation can pass through the stomach and
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`protect 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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`2 A typical representation of such a layered formulation is shown in paragraph 53 of the Sinko
`declaration.
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`acidic environment of the stomach, but permits the coating to dissolve in the less acidic environment
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`of the small intestine, thereby allowing the encapsulated PPI to be released from the drug formulation
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`in the small intestine where it can then be absorbed.
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`27.
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`Various PPis are currently available on the market, with a number available in both
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`branded and generic formulations. The first PPI that became commercially available, omeprazole, was
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`sold under the brand name Prilosec® and has been on the market since 1989. Other PPls, such as
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`lansoprazole (which is sold under the brand name Prevacid®) and esomeprazole (a single enantiomeric
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`form of the racemic drug omeprazole, sold under the brand name Nexium®) subsequently became
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`available. Prevacid® (generically known as lansoprazole) is sold by Takeda, and lost its patent
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`protection in 2009. Dexilant®, the drug at issue in this case, is a variant (i.e., a 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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`28.
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`The pharmaceutical composition disclosed in the '158 patent is made up of two types of
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`enteric-coated particles comprising the PPI dexlansoprazole. (' 158 Pat. Claim 1.) The first particle
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`has an enteric coating that must release the PPI at a 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 a 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 a patient who is on an empty stomach (that is, under fasting conditions), or has eaten at various
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`times (that is, under fed conditions). (Id)
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`29.
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`The '158 patent discloses three strengths of the pharmaceutical composition (30 mg, 60
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`mg, and 90 mg) in Example 1, and the use of one of those strengths, the 90 mg, in Example 2. While
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`Tables 1, 2 and 3 purport to describe the compositions for each of these pharmaceutical formulations,
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`they do not in fact provide any specific example of a particular formulations. Rather, Table 1 lists a
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`range of percentages of polymers that may be used in the enteric coatings of the granules, and Table 2
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`lists ranges of the various excipients, without even naming what the actual excipients should be. For
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`example, Table 1, states that the "proportion of TAK-390 [dexlansoprazole] dose" in granule "LL" can
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`be 15%-50% and in granule "H" can be between 50%-85% of the total dose. Similarly, Table 2 lists
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`ranges for the ingredients in a composition for "Granules-LL," and Table 3 lists ranges for the
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`ingredients in a composition for "Granules-H." The ranges for these ingredients are quite broad and
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`the actual ingredient is not identified specifically, but only by function. For example, the amount of
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`"diluent" can be between 5.0 and 30.0 percent, and no specific diluent is listed. Thus, Example 1
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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 the exact composition of the formulation used in
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`Example 2 cannot be ascertained from the information provided.
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`30.
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`The '158 patent includes an example, Example 2, 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 23 :36-27: 17.) In
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`particular, the pharmaceutical composition was administered to healthy adult subjects under fasting
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`conditions (after an overnight fast), as well as under three fed conditions: 5 minutes before dosing, 30
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`minutes before dosing, and 30 minutes after dosing. (' 158 Pat. at 24: 1-6, Table 4.) Both the plasma
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`concentrations of dexlansoprazole as a function of time, as well as the pHs of the stomach fluids of the
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`subjects, were recorded. (Id at 24:11-45, Tables 5-7.) Based on these collected data, various
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`"pharmacokinetics" 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 effectiveness of the
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`pharmaceutical formulation. (Id)
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`31.
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`"Pharmacokinetics" (sometimes abbreviated as "PK") is a pharmaceutical science that
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`deals with the determination of absorption, distribution, metabolism, and excretion of drugs
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`administered to the body. It is often described as examining the "effect of the body on the drug." This
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`is in contrast to pharmacology, which is a qualitative examination of the "effect of the drug on the
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`body." A more quantitative understanding of the relationship between pharmacokinetics and
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`pharmacology is referred to as "pharmacodynamics" (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 pharmacological 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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`32.
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`These two areas of study, PK and PD, are inextricably connected. The
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`pharmacodynamic properties of a drug are often studied in combination with its pharmacokinetic
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`properties to develop so-called pharmacokinetic/pharmacodynamic (PK/PD) models of the drug in
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`individuals and populations of patients. The pharmacokinetic and pharmacodynamic 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 rate at which those concentrations change. It is
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`for this reason that there is interest in being able to describe the plasma concentration-time profile of a
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`drug following its administration to a patient.
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`33.
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`Following the administration of a drug, for example after oral ingestion, frequent blood
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`samples are obtained for a time sufficient to characterize the entire plasma concentration-time profile.
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`The blood samples or a fluid derived from blood (e.g., plasma or serum) are treated and subjected to an
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`analytical procedure from which one can obtain a quantitative value for the concentration of the drug
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`(and/or metabolites of that drug) in the blood fluid. The resulting concentration-time profiles are then
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`analyzed, either using a computer-based method to obtain a mathematical model that best describes the
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`data, or by a model-independent method. In either approach, estimates of the values of the
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`pharmacokinetic parameters of interest are obtained.
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`34.
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`A 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 (Cmax) achieved is at the peak of
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`the curve, and the time corresponding to that maximum is referred to as Tmax- Also shown in the figure
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`is the total area under 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 a measure related to the amount of drug that gets absorbed into the
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`patient's blood.
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`Time
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`35.
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`The pharmacokinetic parameters Cmax, Tmax, and AUC are reported in Example 2 of the
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`'158 patent for the fasted state as well as for the three fed states noted above. (' 158 Pat. at 24: 11-28;
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`24:62-25:12 and Tables 4, 5 and 6.) 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. (Id.) In addition, the '158 patent discloses the calculation of two pharmacodynamic
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`parameters to determine the effect of food: "mean intragastric pH" and "% time pH>4 over 24 hours
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`post dose." (Id at 24:34-38; 25: 13-27 and Table 7.) The "mean intragastric pH" parameter refers to
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`the statistical mean determined from the pH measurement data. The "% time" parameter refers to the
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`percentage of time that the pH of the stomach fluid is greater than pH 4, over a period of 24 hours after
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`the patient is dosed.
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`8
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`PTX-434.0010
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`Patent Owners' Ex. 2023
`IPR2018-00272
`Page 10 of 21
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`Case5:13-cv-01927-LHK Document88-1 Filed04/24/14 Pagell of 21
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`III.
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`OPINIONS AND BASES THEREFORE
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`A.
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`Person of Ordinary Skill in the Art
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`36.
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`For purposes of my analysis, I have considered how the terms of the' 158 patent would
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`have been understood from the viewpoint of a person of ordinary skill in the art. In my opinion, the art
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`relevant to the claimed subject matter is pharmaceutical drug development and analysis, in particular,
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`clinical pharmacokinetics and clinical pharmacodynamics. A person of ordinary skill in the art would
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`have had a high level of education and skill, including an M.D., a Ph.D. or a Pharm.D. in
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`pharmaceutical sciences, medicine, or a related field, and two years of work experience in the
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`appropriate field, or alternatively, a Bachelor's or Master's Degree and a commensurately greater
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`number of years of experience in the appropriate field.
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`37.
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`I have been asked by counsel to read the claim terms from the perspective of a person
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`of ordinary skill in the art in October 2007, which I understand is the date on which the earliest
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`application that led to the '158 patent was filed. As of October 2007 and at all times since, I would
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`have qualified as a person of at least ordinary skill in the art.
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`B.
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`38.
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`Construction of Disputed Claim Terms of the '158 Patent
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`I understand that Takeda has asserted claims 1-8 of the' 158 patent against the
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`Defendants in this case. Claims 1, 2, 3 and 4 are representative, and read as follows:
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`1. A method of treating heartburn, acid reflux or gastroesophageal
`reflux disease in a patient in need of treatment thereof, the method
`comprising the steps of: a) obtaining a pharmaceutical composition
`comprising dexlansoprazole from a group of pharmaceutical
`compositions comprising proton pump inhibitors; and b) administering
`to a patient suffering from heartburn, acid reflux or gastroesophageal
`reflux, regardless of whether the patient is under fasted or fed
`conditions, a therapeutically effective amount of the pharmaceutical
`composition obtained in step a), wherein the pharmaceutical composition
`comprises: (i) a first solid particle, wherein said first solid particle
`comprises dexlansoprazole and a first enteric coating, wherein the first
`enteric coating releases the proton pump inhibitor from the solid
`particle at a pH of about 5.0 to about 5.5; and (ii) a second solid
`particle, wherein said second solid particle comprises dexlansoprazole
`and a second enteric coating, wherein the second enteric coating
`releases the proton pump inhibitor from the solid particle at a pH of
`about 6.2 to about 6.8; wherein the first solid particle comprises from
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`PTX-434.0011
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`Patent Owners' Ex. 2023
`IPR2018-00272
`Page 11 of 21
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`Case5:13-cv-01927-LHK Document88-1 Filed04/24/14 Page12 of 21
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`about 15% to about 50% by weight of the pharmaceutical composition
`and the second solid particle comprises from about 50% to about 85% by
`weight of the pharmaceutical composition.
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`2. The method of claim 1, wherein the first enteric coating has a pH of
`about 5.5.
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`3. The method of claim 1, wherein the second enteric coating has a pH
`of about 6.75.
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`4. The method of claim 1, wherein the changes in pharmacokinetics
`after administration to the patient of a single dose of a therapeutically
`effective amount of the pharmaceutical composition comprising
`dexlansoprazole under fasting or fed conditions does not produce
`statistically significant changes in intragastric pH.
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`(' 158 patent, Claims 1-4 (disputed phrases bolded).)
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`1.
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`"regardless of whether the patient is under fasted or fed conditions" (claim
`1)
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`Defendants' Construction
`Regardless of whether the patient is dosed
`after an overnight fast, within 5 minutes
`before a meal, within 30 minutes before a
`meal, or within 30 minutes after a meal.
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`Takeda's Construction
`Without regard to food.
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`39.
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`I understand that Defendants originally proposed a construction that defined "fasted or
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`fed conditions" with respect to whether and when a patient has eaten a meal: "whereas the same
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`therapeutic effect is achieved whether the patient has eaten a meal, will eat a meal, or is on an empty
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`stomach." In my opinion, Defendants' original proposed definition was consistent with the
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`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 a high-fat breakfast.
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`(' 158 Pat. at 23 :36-27: 17.) Specifically, the '158 patent includes results for testing conducted on
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`patients "dosed under fasting conditions," "dosed 30 min after the start of a high-fat breakfast," "dosed
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`5 min before a high-fat breakfast," and "dosed 30 min before a high-fat breakfast." (Id at Table 4.)
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`Defendants' original proposed definition covered these various fasted and fed conditions, and further
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`required that the administration of the pharmaceutical dosage form under these conditions should
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`result in the same therapeutic effect.
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`PTX-434.0012
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`Patent Owners' Ex. 2023
`IPR2018-00272
`Page 12 of 21
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`Case5:13-cv-01927-LHK Document88-1 Filed04/24/14 Page13 of 21
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`40.
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`I also understand that in an effort to construe claim terms appearing in different claims
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`in the same way, Defendants have generally agreed to adopt Takeda's proposed construction for
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`"fasting or fed conditions" in connection with its construction of that term in claim 4 of the' 158
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`patent. While Takeda has proposed to define "fasted or fed conditions" in claim 1 to mean "without
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`regard to food," Takeda has defined a nearly identical term - "fasting or fed conditions" - entirely
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`differently in claim 4. (Compare Takeda Br. at 14 with Takeda Br. at 23.) Specifically, in connection
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`with claim 4, Takeda defines "fasting conditions" to mean "dosing after an overnight fast," and "fed
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`conditions" to mean "dosing within 30 minutes before or after a meal" (id at 23), with the latter
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`covering two of the three "fed" conditions disclosed in the' 158 specification. (Id at 24.) But the only
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`difference between the "fast/fed" terms appearing in claims 1 and 4 is the replacement of "fasted' with
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`"fasting" in claim 4. There is no reason why they should be different: the' 158 patent treats these
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`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. 1, Fig. 2, 4:1-4, 24:63-25:65.) Accordingly, the construction for "fasted or
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`fed conditions" in claim 1 should be the same as that for "fasting or fed conditions" in claim 4.
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`41.
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`I also understand that Defendants have slightly modified Takeda's construction for
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`"fasting or fed con di ti ons" to recite each of the three "fed" con di ti ons disclosed in the ' 15 8
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`specification rather than lumping them together as in Takeda' s proposal. Separately reciting each
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`condition is appropriate in the context of claim 1, because the plain meaning of claim 1 requires a
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`therapeutically effective amount of the PPI to be administered irrespective of whether the patient has
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`been dosed under any of the fasted or fed conditions. (Exhibit C defines "regardless" as "without
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`regard to, irrespective of") In other words, the "regardless" term in claim 1 requires a therapeutic
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`effect to be achieved no matter which state the patient is in: 30 minutes after eating, 5 minutes before
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`eating, or 30 minutes before eating. ('158 Pat. at Table 4.)
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`PTX-434.0013
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`Patent Owners' Ex. 2023
`IPR2018-00272
`Page 13 of 21
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`Case5:13-cv-01927-LHK Document88-1 Filed04/24/14 Page14 of 21
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`42.
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`Consistent with this requirement, Defendants' proposed definition separately identifies
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`the fasted state, the fed state after the start of a meal, and the two fed states before the start of a meal,
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`to indicate that the therapeutic results must be achieved no matter which of these states the patient is in
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`when dosed with the drug. This construction is consistent with the specification, which defines
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`"fasted" to mean "after an overnight fast(' 158 Pat. at 23 :63-24:4), and further defines three "fed"
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`conditions: patient is dosed within 30 minutes after a meal, within 5 minutes before a meal, or within
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`30 minutes before a meal. (' 158 Pat. at Table 4.) This construction is also consistent with the patent's
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`statements distinguishing the invention from previously-available PPls, which according to the patent
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`should be taken shortly before eating a meal. (' 158 Pat. at 2:4-15, 9:66-10:34.)
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`2.
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`"enteric coating releases the proton pump inhibitor from the solid particle
`at a pH or' "about 5.0 to about 5.5" or "about 6.2 to about 6.8" ( claim 1)
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`Defendants' Construction
`Enteric coating releases all of the proton
`pump inhibitor from the solid particle at a pH
`of [no less than 4.95 to a pH of no more than
`5.55]/ [no less than 6.15 to a pH of no more
`than 6.85].
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`Takeda's 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.
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`43.
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`Defendants' proposed construction has two parts: (1) the enteric coating must release
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`all of the proton inhibitor, and (2) the pH at which the release takes place must be "about 5.0 to about
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`5.5" or "about 6.2 to about 6.8," where "about" is defined to mean 0.05 pH units. Once this definition
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`of "about" is applied to the pH levels recited in the claims, the pH ranges become "no less than 4.95 to
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`no more than 5.55" and "no less than 6.15 to no more than 6.85." In my opinion, Defendants'
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`proposed construction is consistent with the intrinsic and extrinsic evidence.
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`PTX-434.0014
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`Patent Owners' Ex. 2023
`IPR2018-00272
`Page 14 of 21
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`Case5:13-cv-01927-LHK Document88-1 Filed04/24/14 Page15 of 21
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`a.
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`"enteric coating releases the proton pump inhibitor .. at3 a pH or'
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`44.
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`Defendants' proposed construction requires that the enteric coating surrounding the PPI
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`actually releases its PPI at or above a particular pH. This construction is consistent with the intrinsic
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`evidence, in particular the claim language, which requires release of the PPI: "enteric coating releases
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`the proton pump inhibitor ... at a pH of .... " (' 158 Pat. at Claim 1.) Defendants' construction is also
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`consistent with the specification: "wherein the first enteric coating releases the active agent from the
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`solid particle at a pH of about 5.0 to about 5.5," and "wherein the second enteric coating releases the
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`active agent from the solid particle at a pH of about 6.2 to about 6.8," "[t]he second enteric coating
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`surrounds the core and releases the active agent from the solid particle at a pH of about 6.2 to about
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`6.8." (' 158 Pat. at 2:36-45; 12:24-36 (emphases added).)
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`45.
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`In contrast, Takeda's proposed construction reads the "release" requirement entirely out
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`of the claims while at the same time readi