UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`LUPIN LIMITED AND LUPIN PHARMACEUTICALS INC.
`Petitioners
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`v.
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`iCEUTICA PTY LTD.
`Patent Owner
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`Case IPR2016-00399
`Patent 9,017,721
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`PATENT OWNER iCEUTICA’s
`PRELIMINARY RESPONSE
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`

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`Case IPR2016-00399
`Attorney Docket No: 31215-0011IP4
`TABLE OF CONTENTS
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`INTRODUCTION ................................................................................ 1
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`BACKGROUND .................................................................................. 4
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`I. 
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`II. 
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`III.  THE ‘721 PATENT .............................................................................. 9
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`A. 
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`The ‘721 patent discloses diclofenac acid solid oral unit doses
`having improved dissolution profiles ......................................... 9
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`IV.  CLAIM CONSTRUCTION ............................................................... 16
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`B. 
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`C. 
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`Particle size alone does not dictate the dissolution profile of the
`diclofenac acid solid oral unit dose .......................................... 10
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`The ‘721 patent relies on a test for measuring the dissolution
`profile of a given diclofenac acid solid oral unit dose ............. 10
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`D.  During prosecution, the Examiner relied on the dissolution
`profile in allowing the ‘721 patent claims ............................... 12
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`A. 
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`The dissolution profile is entitled to patentable weight ........... 17
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`1.  The dissolution profile defines the diclofenac acid-
`containing solid oral unit dose that is the subject of the claimed
`composition .............................................................................. 18
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`2.  The ‘721 patent specification and prosecution history
`demonstrate that the dissolution profile is “an integral part of
`the invention” ........................................................................... 22
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`3.  The dissolution profile is not a necessary consequence of
`particle size ............................................................................... 24
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`4.  The dissolution profile is not an optional condition in the
`claims ....................................................................................... 26
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`5.  Giving the dissolution profile patentable weight is
`consistent with the District Court of Delaware’s construction of
`the claims .................................................................................. 27 
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`Case IPR2016-00399
`Attorney Docket No: 31215-0011IP4
`CLAIMS 1-24 ARE PATENTABLE OVER MEISER IN VIEW OF
`THE NOVARTIS PACKAGE INSERT ............................................ 28
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`Claims 1-24 are not obvious over Meiser in view of the
`Novartis Package Insert ............................................................ 29
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`Claims 1-24 are not obvious over Meiser in view of the
`Novartis Package Insert, USP, and Chuasuwan ....................... 32
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`1.  The obviousness of the test conditions is irrelevant ......... 34
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`2.  Meiser’s diclofenac acid particles would not inherently
`have the dissolution profile in the ‘387 claims measured under
`the conditions disclosed in USP and Chuasuwan .................... 35
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`Claims 1-24 are not obvious over Meiser in view of the
`Novartis Package Insert, USP, Chuasuwan, and Reiner .......... 39
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`A. 
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`B. 
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`C. 
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`V. 
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`VI.  CONCLUSION .................................................................................. 41 
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`Case IPR2016-00399
`Attorney Docket No: 31215-0011IP4
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`LIST OF EXHIBITS
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`2002
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`Exhibit No. Description
`2001
`Lupin’s Answering Claim Construction Brief, C.A. No. 14-
`1515-SLR-SRF (Dec. 4, 2015)
`Amiji Declaration submitted in support of Lupin’s
`Answering Claim Constr. Br., C.A. No. 14-1515-SLR-SRF
`(Dec. 4, 2015)
`Deposition of Mansoor Amiji, R.Ph., Ph.D.(December 18,
`2015)
`Memorandum Order, C.A. No. 14-1515-SLR-SRF (February
`29, 2016)
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`2003
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`2004
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`Case IPR2016-00399
`Attorney Docket No: 31215-0011IP4
`TABLE OF AUTHORITIES
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`CASES
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` Page(s)
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`KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) ........ 3, 28, 31, 41
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`In re Cuozzo Speed Techs., LLC, No. 2014-1301, slip op. at
`10-19 (Fed. Cir. 2015) ....................................................................... 16
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`In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
`2007) .................................................................................................. 16
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`Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 1330 (Fed.
`Cir. 2005) ..................................................................................... 18, 22
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`In re Kao, 639 F.3d 1057, 1061-62, 1066-67 (Fed. Cir.
`2011) ................................................................................ 19, 20, 27, 34
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`Dell, Inc. v. Acceleron, LLC, No. 2015-1513, -1514, slip op.
`at 11-12 (Fed. Cir. Mar. 15, 2016) .................................................... 26
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`In re Oelrich, 666 F.2d 578, 581-82 (C.C.P.A. 1981) ..................... 29, 38
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`Santarus Inc. v. Par Pharm. Inc., 694 F.3d 1344, 1354 (Fed.
`Cir. 2012) ........................................................................................... 35
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`Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 999
`(Fed. Cir. 2006) ................................................................................. 39
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`REGULATIONS
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`35 U.S.C. § 103 .................................................................................... 2, 29
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`35 U.S.C. § 112 ........................................................................................ 12
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`37 C.F.R. § 42.100(b) ............................................................................. 16
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`PTAB DECISIONS
`Ex Parte Berzofsky, Appeal No. 2010-011270, 2011 WL
`891756 (BPAI March 10, 2011) ................................................... 20, 21
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`Attorney Docket No: 31215-0011IP4
`Dr. Reddy’s Laboratories, Ltd. v. Galderma Laboratories,
`Inc., IPR2015-01777, slip op. at 18 (PTAB Feb. 16,
`2016) ............................................................................................ 31, 41
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`Case IPR2016-00399
`Attorney Docket No: 31215-0011IP4
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`I.
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`INTRODUCTION
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`U.S. Patent No. 9,017,721 (“the ‘721 patent”) claims a solid oral unit dose
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`(e.g., a tablet or capsule) of a composition containing diclofenac acid formulated to
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`have a certain dissolution profile when tested in vitro according to an accepted test
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`method. The ‘721 patent reflects the inventors’ discovery that diclofenac acid-
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`containing solid oral unit doses having the claimed dissolution profile and particle
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`size have improved solubility relative to existing diclofenac solid oral unit doses
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`such as the diclofenac acid salt-containing tablets that Novartis markets. See
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`Novartis Package Insert (EX. 1006); the ‘721 patent (EX. 1001), 54:46 to 55:32
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`(Example 14). As a result, lower doses of diclofenac acid can be used, while
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`maintaining efficacy. See the ‘721 patent, 3:5-17.
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`Lupin challenges the patentability of the ‘721 patent claims on three
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`grounds. The first ground is based upon an improper claim interpretation that
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`ignores the dissolution profile recited in each claim. Under the broadest reasonable
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`interpretation of claims 1-24, the dissolution profile limits the claims by defining
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`the diclofenac acid-containing solid oral unit doses for administration to a patient.
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`The dissolution profile is material to the patentability of claims 1-24; thus, it
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`cannot be ignored, as Lupin urges.
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`The remaining two grounds afford patentable weight to the dissolution
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`profile. However, in each ground Lupin mistakenly focuses on whether the choice
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`Case IPR2016-00399
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`of test conditions for measuring dissolution rate would have been obvious. The
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`obviousness of the test conditions is irrelevant. The purpose of the test is to
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`compare different diclofenac acid-containing solid oral unit doses. Lupin and its
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`expert, Dr. Amiji, have admitted that not all diclofenac acid-containing solid oral
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`unit doses will have the dissolution profile recited in the claims. See EX. 2001, p.
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`26; EX. 2002, p. 23, ¶ 82; and EX. 2003, p. 11, 41:18-42:1. This is because many
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`factors influence dissolution profile, including the nature of the drug itself, particle
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`size, and the excipients includes in the solid oral unit dose.
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`The question under 35 U.S.C. § 103 is whether diclofenac acid-containing
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`solid oral unit doses having the dissolution profile, particle size, and amount of
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`diclofenac acid recited in the claims would have been obvious. Lupin relies on
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`Meiser (EX. 1005) as its primary reference. Lupin then proposes to combine
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`Meiser with the Novartis Package Insert (EX. 1006), USP (EXS. 1007 and 1008),
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`Chuasuwan (EX. 1009), and Reiner (EX. 1010).
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`Meiser describes milling biologically active compounds, including
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`diclofenac acid, to produce drug particles in a certain size range. Lupin and Dr.
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`Amiji have admitted that particle size alone does not dictate dissolution profile.
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`See EX. 2001, p. 26; EX. 2002, p. 23, ¶ 82; and EX. 2003, p. 11, 41:18 to 42:1.
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`Three of the secondary references (Novartis Package Insert, Chuasuwan, and
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`Reiner) describe diclofenac salts. Salts represent an entirely different approach to
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`Attorney Docket No: 31215-0011IP4
`solving the solubility problem. Lupin fails to offer a reasoned explanation as to
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`why a person of ordinary skill would have been motivated to design a diclofenac
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`acid-containing solid oral unit dose having the dissolution properties recited in the
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`claims by combining a reference describing milling diclofenac acid (Meiser) with
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`references describing diclofenac salts (Novartis Package Insert, Chuasuwan,
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`Reiner). See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) (obviousness
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`requires an “articulated reasoning with some rational underpinning” for combining
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`references).
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`The remaining secondary reference, USP, merely discloses dissolution test
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`conditions similar to the conditions recited in the ‘387 patent claims. Thus, it is
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`not relevant to the obviousness issue, when properly framed.
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`Lupin also relies on a flawed inherency theory in Grounds II and III based
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`upon alleged admissions by iCeutica and its exclusive licensee, Iroko. Lupin
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`misconstrues statements that iCeutica and Iroko made. They do not prove that
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`Meiser necessarily discloses diclofenac acid-containing solid oral unit doses
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`having the dissolution properties, particle size, and amount of diclofenac acid that
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`the ‘721 patent claims require.
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`For at least these reasons, Lupin has failed to demonstrate a reasonable
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`likelihood that claims 1-24 of the ‘721 patent are unpatentable as obvious. Lupin’s
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`petition, therefore, should be denied.
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`Case IPR2016-00399
`Attorney Docket No: 31215-0011IP4
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`II. BACKGROUND
`“Bioavailability” is the rate and extent to which a drug becomes available to
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`target tissue in the body following administration. The ‘387 patent (EX. 1001),
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`1:32-36. Factors that affect bioavailability include “the form of dosage and the
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`solubility and dissolution rate of the active material.” Id., 1:36-38. A number of
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`drugs are poorly soluble in water at physiological pH. Id., 1:28-32. Such drugs
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`“tend to be eliminated from the gastrointestinal tract before being absorbed into the
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`circulation.” Id., 1:39-41.
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` Diclofenac acid belongs to a class of drugs known as non-steroidal anti-
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`inflammatory drugs (“NSAIDS”). Diclofenac acid and its salts are used to treat
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`acute and chronic pain. Id., 3:7-8. Like many NSAIDS, diclofenac acid has poor
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`solubility in water at physiological pH. Consequently, dissolution and absorption
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`into the body are slow. Id., 3:10-11; Amiji Decl’n (EX. 1002), ¶ 20
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`(“[D]iclofenac’s poor water solubility becomes the rate-limiting factor in its oral
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`bioavailability.”).
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`A number of approaches have been developed to improve the dissolution
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`profile of poorly soluble drugs. One approach involves preparing a salt of the
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`active agent. The ‘721 patent (EX. 1001), 1:66-67; Amiji Decl’n (EX. 1002), ¶ 21
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`(“To improve solubility, diclofenac is often formulated as a sodium or potassium
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`salt, thus overcoming the pH-dependent solubility issues”). Novartis, for example,
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`used this approach to prepare tablets containing salts of diclofenac acid. The
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`tablets, which are dispensed under the trade names Cataflam®, Voltaren®, and
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`Voltaren®-XR, are described in the Novartis Package Insert (EX. 1006) upon
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`which Lupin relies in its Petition. See Amiji Decl’n (EX. 1002), ¶ 16 (“The
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`Novartis Package Insert discloses two solid dosage forms of diclofenac, the sodium
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`or potassium salt known as Voltaren or Cataflam, respectively.”). Two of the other
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`references upon which Lupin relies, Chuasuwan (EX. 1009) and Reiner (EX.
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`1010), similarly describe preparing salts of diclofenac acid to improve dissolution
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`profile.
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`One problem with salts, as Lupin acknowledges in its Petition, is that they
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`can alter the pharmaceutical activity of the drug. Petition, p. 6, citing Samejima
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`(EX. 1016) (“Per Samejima, these methods each suffer from drawbacks, including
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`altering pharmaceutical activity of a drug (as is the case with salts) ….”). In the
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`case of diclofenac, Lupin’s own expert, Dr. Amiji, admits that while the salts
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`dissolve better in water, they are “less readily absorbed in the GI tract as compared
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`to the neutral diclofenac acid molecule, according to the pH-partition principle.”
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`Amiji Decl’n (EX. 1002), ¶ 22, citing EX. 1035 at 715-716.
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`An alternative approach for generally improving dissolution profile includes
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`converting the drug into an amorphous state, e.g., through “micronization,
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`modification of crystal or polymorphic structure, development of oil based
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`solutions, use of co-solvents, surface stabilizers or complexing agents, micro-
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`emulsions, supercritical fluid and production of solid dispersions or solutions.”
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`The ‘721 patent (EX. 1001), 2:6-10. However, as the ‘721 patent explains, these
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`techniques are unpredictable and have drawbacks, including complexity and
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`difficulty in removing contaminants, as well as stability and re-crystallization
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`issues. Id., 2:14-24.
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`Another possible approach for improving dissolution profile includes
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`reducing particle size through, e.g., formation of microcapsules, wet milling, or dry
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`milling. Id., 1:50-64 and 2:25-65. Although still unpredictable, reducing particle
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`size increases surface area of the drug particles, which, in turn, may improve the
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`dissolution profile for certain drugs. Id., 1:45-50. Meiser (EX. 1005), the primary
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`reference upon which Lupin relies, describes dry milling drugs, including
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`diclofenac and raloxifene, to reduce particle size. Meiser (EX. 1005), pp. 59-61
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`and 68-70. In the case of diclofenac, Meiser specifically describes dry milling
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`diclofenac acid with sodium chloride or ammonium chloride as a grinding agent,
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`and then removing the grinding agent to create diclofenac acid particles. Meiser
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`(EX. 1005), pp. 68-69 and 70-71.
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`Although particle size affects dissolution profile, it is not the only factor that
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`determines dissolution profile. This is particularly true when the milled
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`composition has been processed further to create a solid oral unit dosage form such
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`as a tablet or capsule. Lupin itself has admitted that other factors influence
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`dissolution profile. In a Markman brief it submitted in the related district court
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`litigation between iCeutica and Lupin, Lupin argued (emphasis added):
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`Furthermore, the specific pharmaceutical composition is important for
`achieving the claimed dissolutions. Modifying the composition,
`including the active ingredient, the particle size, and the excipients,
`would affect the dissolution. Amiji, ¶ 82. As discussed above in
`Section III.B.2., the diclofenac capsules test in Example 14 [of the
`‘387 patent] were dry milled with 84% lactose monohydrate and 1%
`sodium lauryl sulfate. Changing the type or quantity of surfactant
`will change the dissolution profile of the pharmaceutical
`composition. See, e.g., Ex. D (Kessisoglou at 632; Ex. 11 (Rohrs at
`2); Amiji ¶ 82.1
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`Lupin relied on the testimony of Dr. Amiji, who opined:
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`82. The components of the pharmaceutical composition will also alter
`the extent and rate of dissolution. Of course, the properties of the
`active ingredient, including its particle size, will affect the dissolution
`profile.2
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`1 Lupin’s Answering Claim Constr. Br. (EX. 2001), p. 26.
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`2 Amiji Declaration submitted in support of Lupin’s Answering Claim Constr. Br.
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`(EX. 2002), p. 23, ¶ 82.
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`Dr. Amiji later confirmed his opinion that particle size was not the only
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`factor that influenced dissolution profile. In a deposition taken in the related
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`district court litigation between iCeutica and Lupin, Dr. Amiji testified:
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`Q. You state in paragraph 82, “The components of the
`pharmaceutical composition will also alter the extent and rate of
`dissolution. Of course, the properties of the active ingredient,
`including its particle size, will affect the dissolution profile. Also, the
`excipients formulated with the pharmaceutical composition will affect
`the dissolution profile.” Do you see that?
`A. Yes.
`Q. Did you believe those statements to be true when you wrote
`your declaration?
`A. Yes.
`Q. Do you believe those statements to be true still today?
`A. Yes.3
`Lupin’s admission, supported by its expert, that particle size alone does not
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`determine dissolution profile is important. As discussed in detail below, this
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`admission contradicts Lupin’s arguments in its IPR Petition that particle size
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`dictates dissolution profile. To the contrary, the composition of the drug itself
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`(e.g., acid vs. salt), as well as the particular excipients included in a solid oral unit
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`dosage form of the drug, also affect dissolution profile.
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`3 Deposition of Mansoor Amiji, R.Ph., Ph.D.-December 18, 2015 (EX. 2003), p.
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`11, 41:18 to 42:1.
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`Case IPR2016-00399
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`III. THE ‘721 PATENT
`A. The ‘721 patent discloses diclofenac acid solid oral unit doses having
`improved dissolution profiles
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`The ‘721 patent covers a solid oral unit dose of a composition containing
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`diclofenac acid, a poorly water-soluble analgesic. The composition itself is
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`formulated to have a certain particle size range and a particular dissolution profile
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`when tested in vitro according to a defined test protocol. See, e.g., the ‘721 patent
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`(EX. 1001), 54:46 to 55:32 (Example 14). Improving the dissolution profile of
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`diclofenac acid, and thus its bioavailability, makes it possible to use lower doses of
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`diclofenac relative to conventional diclofenac formulations. Id., 38:66 to 39:2
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`(“The diclofenac compositions of the invention preferably exhibit increased
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`bioavailability (AUC) and require smaller doses as compared to prior conventional
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`compositions administered at the same dose”). Lowering the dose minimizes the
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`side effects of diclofenac acid, which can include increased risk of gastrointestinal
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`bleeding and cardiovascular side effects. See Chuasuwan (EX. 1009), p. 1208;
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`Amiji Decl’n (EX. 1002), ¶ 18.
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`The compositions disclosed in the ‘721 patent enable the use of diclofenac
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`acid, rather than one of its salts. As discussed in Section II, supra, pharmaceutical
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`companies such as Novartis chose to address the solubility issue by converting
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`diclofenac acid to a sodium or potassium salt. Novartis Package Insert (EX. 1006);
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`Amiji Decl’n (EX. 1002), ¶ 16 (“The Novartis Package Insert discloses two solid
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`dosage forms of diclofenac, the sodium or potassium salt known as Voltaren or
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`Cataflam, respectively”). While salts improve water solubility, they also alter the
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`pharmacological properties of the active agent. See Amiji Decl’n (EX. 1002), ¶ 22,
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`citing EX. 1035 at 715-716 (while diclofenac acid salts dissolve better in water,
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`they are “less readily absorbed in the GI tract as compared to the neutral diclofenac
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`acid molecule, according to the pH-partition principle.”).
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`B. Particle size alone does not dictate the dissolution profile of the
`diclofenac acid solid oral unit dose
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`One feature of the diclofenac acid compositions claimed in the ‘721 patent is
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`that the diclofenac acid has a median particle size, on a volume average basis, of
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`between 25 and 1000 nm. Id., 4:12-14. As Lupin and its expert, Dr. Amiji,
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`acknowledge, however, the particle size alone does not dictate dissolution profile.
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`Other factors also influence, including the composition of the drug itself (e.g., acid
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`vs. salt), as well as the particular excipients included in a solid oral unit dosage
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`form of the drug (e.g., milling agents, surfactants, and the like). See EXS. 2001, p.
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`26; 2002, p. 23, ¶ 82; and 2003, p. 11, 41:18 to 42:1.
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`C. The ‘721 patent relies on a test for measuring the dissolution profile
`of a given diclofenac acid solid oral unit dose
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`The ‘721 patent states the following with respect to measuring the
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`dissolution profile:
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`Standard methods for determining the dissolution profile of a material
`in vitro are available in the art. A suitable method to determine an
`improved dissolution profile in vitro may include determining the
`concentration of the sample material in a solution over a period of
`time and comparing the results from the sample material to a control
`sample.
`The ‘721 patent (EX. 1001), 24:55-61.
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`The claims of the ‘721 patent set forth a specific in vitro test for measuring
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`the dissolution profile of a given diclofenac acid solid oral unit dosage:
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`the unit dose, when tested in vitro by USP Apparatus I (Basket)
`method of U.S. Pharmacopoeia at 100 rpm, at 37º C. in 900 ml of
`0.05% sodium lauryl sulfate in citric acid solution to pH 5.75, has a
`dissolution rate of diclofenac acid such that at least 94%, by weight, is
`released by 75 minutes.4
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`Example 14 of the ‘721 patent uses this particular test to compare the
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`dissolution profile of a diclofenac acid composition in the form of a tablet with a
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`Novartis diclofenac salt tablet (Voltarol®). The ‘721 patent (EX. 1001), 54:62 46
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`to 55:49 32. Even though salts were thought to be more soluble than acids, the test
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`results demonstrated that the ‘721 patent’s diclofenac acid tablet had an improved
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`4 ‘721 patent, claim 1. Claim 8, the other independent claim, recites that at least
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`95%, by weight, is released by 75 minutes.
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`dissolution profile relative to Novartis’ commercial diclofenac salt tablet. Id.,
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`55:1-16 (Table 14a).
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`Lupin acknowledges that the test protocol set forth in Example 14 and the
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`‘721 patent claims is a reliable protocol for measuring dissolution profile. Lupin
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`states that the test conditions come from United States Pharmacopeia (USP) and
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`FDA guidelines. Petition, pp. 17-20; EX. 1007 (USP <711> guidelines); EX. 1008
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`(USP <1092> guidelines); EX. 1025 (FDA Guidance). Lupin goes so far as to
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`characterize the protocol as a “run-of-the-mill dissolution test.” Petition, p. 29.
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`Lupin’s characterization of the test protocol demonstrates that it was a reasonable
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`choice for describing the claimed diclofenac acid solid oral unit dose formulations,
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`and distinguishing them from other formulations that did not meet the threshold
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`dissolution rate when measured under the conditions defined in the test protocol.
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`See 35 U.S.C. § 112, para. 2 (claims must “particularly point[ing] out and
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`distinctly claim[ing] the subject matter which the applicant regards as his
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`invention”).
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`D. During prosecution, the Examiner relied on the dissolution profile in
`allowing the ‘721 patent claims
`
`
`During prosecution, iCeutica filed a preliminary amendment that presented
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`application claims 72-99 for consideration. EX. 1027, pp. 158-62. The two
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`independent claims, application claims 42 and 51, recited a unit dose of a
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`pharmaceutical composition containing either 18 mg (claim 42) or 35 mg (claim
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`51) of diclofenac acid. Id., pp. 159-160. Dependent claims 43 and 52, which
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`depended on claims 42 and 51, respectively, recited the dissolution profile
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`requirement currently found in issued independent claims 1 and 8. See id.
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`Dependent claims 44 and 53, which depended on claims 42 and 51, respectively,
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`required the diclofenac acid to have a median particle size, on a volume average
`
`basis, of less than 1000 nm and greater than 25 nm. Id.
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`In an Office Action mailed May 14, 2014, the Examiner rejected all claims
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`as obvious over Meiser (EX. 1005) in combination with Reiner (EX. 1010). Id.,
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`pp. 176-78. Lupin relies on the same two references in its IPR Petition, and uses
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`Meiser as its main reference. The Examiner acknowledged that Meiser failed to
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`teach a unit dosage composition containing either 18 or 35 mg of diclofenac acid,
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`as application claims 42 and 51 required. Id., p. 177. With respect to claims 43
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`and 52, which recited the dissolution profile requirement, the Examiner stated:
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`Since Meiser is drawn to the same particle sizes as the instantly
`claimed invention, and Reiner teaches diclofenac acid as an
`acceptable form of diclofenac, the claimed particles must necessarily
`have the same dissolution properties as the particles taught by the
`prior art of Meiser and Reiner as combined.
`Id., p. 178.
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`In response to the Office Action, iCeutica amended claims 42 and 51 to
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`recite a median particle size, on a volume average basis, of less than 1000 nm and
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`greater than 25 nm. Id., pp. 200-01. iCeutica also amended dependent claims 43
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`and 52, converting them into independent claims that recited a solid oral unit dose
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`of a pharmaceutical composition containing, respectively, 18 mg and 35 mg of
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`diclofenac acid, along with dissolution profiles.
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`iCeutica also added dependent claims 74 and 75, which depended on claims
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`43 and 52, respectively, and recited median particle size, on a volume average
`
`basis, of less than 800 nm and greater than 25 nm. Id., pp. 235. Claims 74 and 75
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`correspond to issued patent claims 1 and 8, respectively, and recite both a particle
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`size range and dissolution properties. iCeutica also argued that the pending claims
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`were not obvious over Meiser plus Reiner:
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`The present specification presents the results of clinical studies on the
`pharmacodynamics characteristics of diclofenac dosage forms within
`the present claims. It cannot be predicted that by reducing the particle
`size of diclofenac acid that dosage forms with the specific desirable
`characteristics of those claimed could be achieved.
`Id., p. 203.
`
`
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`In an Office Action mailed January 15, 2015, the Examiner stated that
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`claims 74 and 75, which recited specific median particle sizes, would be allowable
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`on the ground that these claims were commensurate with the unexpected results
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`iCeutica had presented:
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`The composition of claims 74 and 75 is patentable over the cited prior
`art since the composition provides the advantage of using a lower
`dose of diclofenac acid to achieve an unexpectedly higher dissolution
`rate of diclofenac acid in aqueous medium through the use of the
`marginally water-soluble diclofenac acid in the form of nanoparticles.
`Id., p. 248.
`
`
`
`In response, iCeutica amended independent claims 42 and 51 to incorporate
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`dissolution profiles, in addition to the dose and median particle size of diclofenac
`
`acid. Dependent claims were amended to depend on claims 42 and 51. Claims 42
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`and 51 issued as patent claims 1 and 8, respectively.
`
`
`
`The Examiner’s decision to allow claims 42 and 51, which required a
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`particular dissolution profile, while continuing to reject claims that recited only a
`
`certain particle size range, demonstrate he recognized that particle size alone did
`
`not determine dissolution profile. On the contrary, as Lupin and Dr. Amiji have
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`admitted, many other factors play a role in determining the dissolution profile. The
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`Examiner’s decision further demonstrates that he considered, and ultimately
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`withdrew, unpatentability grounds that are indistinguishable from the grounds that
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`Lupin raises in its IPR Petition.
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`IV. CLAIM CONSTRUCTION
`Claims are interpreted using the “broadest reasonable construction in light of
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`the specification of the patent in which [they] appear[].” 37 C.F.R.§ 42.100(b); see
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`also In re Cuozzo Speed Techs., LLC, No. 2014-1301, slip op. at 10–19 (Fed. Cir.
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`2015). Under the broadest reasonable construction standard, claim terms are given
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`their ordinary and customary meaning, as would be understood by one of ordinary
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`skill in the art at the time of the invention. In re Translogic Tech., Inc., 504 F.3d
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`1249, 1257 (Fed. Cir. 2007).
`
`Claim 1 reads as follows (paragraph structure added for clarity):
`
`1. A solid oral unit dose of a pharmaceutical composition
`containing 18 mg of diclofenac acid,
`wherein the diclofenac acid has a median particle size, on a
`volume average basis, of less than 1000 nm and greater than 25 nm,
`wherein the unit dose, when tested in vitro by USP Apparatus I
`(Basket) method of U.S. Pharmacopoeia at 100 rpm, at 37º C. in 900
`ml of 0.05% sodium lauryl sulfate in citric acid solution to pH 5.75,
`has a dissolution rate of diclofenac acid such that at least 94%, by
`weight, is released by 75 minutes.
`
`Independent claim 8 is similar except that it recites a solid oral unit dose
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`containing 35 mg of diclofenac acid, and requires a diclofenac acid dissolution rate
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`of at least 95%, by weight, after 75 minutes.
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`Patent Owner proposes a construction for the following term: “wherein the
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`unit dose, when tested in vitro by USP Apparatus I (Basket) method of U.S.
`
`Pharmacopoeia at 100 rpm, at 37º C. in 900 ml of 0.05% sodium lauryl sulfate in
`
`citric acid solution to pH 5.75, has a dissolution rate of diclofenac acid such that at
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`least X%, by weight, is released by Y minutes.” For convenience, we will refer
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`this term as “the dissolution profile.” All other terms should be construed
`
`according to their ordinary and customary meaning.
`
`A. The dissolution profile is entitled to patentable weight
`
`The dissolution profile defines the diclofenac acid-containing solid oral unit
`
`dose functionally in terms of its dissolution properties measured under certain test
`
`conditions identified in the claims. Specifically, it requires the diclofenac acid-
`
`containing solid oral unit dose to release a certain amount of diclofenac acid within
`
`a certain period of time when “tested in vitro USP Apparatus I (Basket) method of
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`U.S. Pharmacopoeia at 100 rpm, at 37ºC. in 900 ml of 0.05% sodium lauryl sulfate
`
`in citric acid solution to pH 5.75.” In the case of independent claim 1, the
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`diclofenac acid-containing solid oral unit dose must release at least 94% diclofenac
`
`acid, by weight, by 75 minutes. In the case of independent claim 8, the diclofenac
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`acid-containing solid oral unit dose must release at least 95% diclofenac acid, by
`
`weight, by 75 minutes.
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`The broadest reasonable interpretation of the ‘721 patent’s composition is
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`that the dissolution profile affirmatively limits the claims by defining the
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`diclofenac acid-containing solid oral unit doses that are administered for treating
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`pain. The dissolution profile, therefore, is entitled to patentable weight. It can