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 IPR2016-00397
`Patent 8,999,387
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`PATENT OWNER iCEUTICA’s
`PRELIMINARY RESPONSE
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`Case IPR2016-00397
`Attorney Docket No: 31215-0011IP3
`TABLE OF CONTENTS
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`INTRODUCTION ................................................................................ 1
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`II. 
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`III.  BACKGROUND .................................................................................. 4
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`IV.  THE ‘387 PATENT .............................................................................. 9
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`A. 
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`The ‘387 patent discloses diclofenac acid solid oral unit doses
`having improved dissolution profiles ......................................... 9
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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 ‘387 patent relies on a test for measuring the dissolution
`profile of a given diclofenac acid solid oral unit dose ............. 11
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`D.  During prosecution, the Examiner relied on the dissolution
`profile in allowing the ‘387 patent claims ............................... 13
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`CLAIM CONSTRUCTION ............................................................... 15
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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
`method for treating pain ........................................................... 18
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`2.  The ‘387 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 ............................................................................... 25
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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 .................................................................................. 28 
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`V. 
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`Case IPR2016-00397
`Attorney Docket No: 31215-0011IP3
`VI.  CLAIMS 1-24 ARE PATENTABLE OVER MEISER IN VIEW OF
`THE NOVARTIS PACKAGE INSERT ............................................ 29
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`A. 
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`B. 
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`C. 
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`Claims 1-24 are not obvious over Meiser in view of the
`Novartis Package Insert ............................................................ 30
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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 .......... 40
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`VII.  CONCLUSION .................................................................................. 42 
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`Case IPR2016-00397
`Attorney Docket No: 31215-0011IP3
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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 IPR2016-00397
`Attorney Docket No: 31215-0011IP3
`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, 29, 32, 34, 41
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`In re Cuozzo Speed Techs., LLC, No. 2014-1301, slip op. at
`10-19 (Fed. Cir. 2015) ................................................................. 15, 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) ................................................................................ 18, 19, 20, 27
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`Microprocessor Enhancement Corp. v. Texas Instruments,
`Inc., 520 F.3d 1367, 1374 (Fed. Cir. 2008) ................................. 19, 20
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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) ..................... 30, 39
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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, 30
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`35 U.S.C. § 112 .................................................................................. 12, 13
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`37 C.F.R. § 42.100(b) ............................................................................. 15
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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: 31215-0011IP3
`Dr. Reddy’s Laboratories, Ltd. v. Galderma Laboratories,
`Inc., IPR2015-01777, slip op. at 18 (PTAB Feb. 16,
`2016) ............................................................................................ 32, 41
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`Case IPR2016-00397
`Attorney Docket No: 31215-0011IP3
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`I.
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`INTRODUCTION
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`U.S. Patent No. 8,999,387 (“the ‘387 patent”) claims methods for treating
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`pain by administering a solid oral unit dose (e.g., a tablet or capsule) of a
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`composition containing diclofenac acid formulated to have a certain dissolution
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`profile when tested in vitro according to an accepted test method. The ‘387 patent
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`reflects the inventors’ discovery that diclofenac acid-containing solid oral unit
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`doses having the claimed dissolution profile and particle size have improved
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`solubility relative to existing diclofenac solid oral unit doses such as the diclofenac
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`salt-containing tablets that Novartis markets. See Novartis Package Insert (EX.
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`1006); the ‘387 patent (EX. 1001), 54:62 to 55:49 (Example 14). As a result,
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`lower doses of diclofenac acid can be used, while maintaining efficacy. See the
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`‘387 patent, 3:4-17.
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`Lupin challenges the patentability of the ‘387 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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`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 to 42:1. This is because
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`many factors influence dissolution profile, including the nature of the drug itself,
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`particle 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 it would have been obvious
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`to treat pain using diclofenac acid-containing solid oral unit doses having the
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`dissolution profile, particle size, and amount of diclofenac acid recited in the
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`claims. Lupin relies on Meiser (EX. 1005) as its primary reference. Lupin then
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`proposes to combine Meiser with the Novartis Package Insert (EX. 1006), USP
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`(EXS. 1007 and 1008), 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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`Attorney Docket No: 31215-0011IP3
`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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`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 ‘387 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 ‘387 patent are unpatentable as obvious. Lupin’s
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`petition, therefore, should be denied.
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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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`1:30-34. Factors that affect bioavailability include “the form of dosage and the
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`solubility and dissolution rate of the active material.” Id., 1:34-36. A number of
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`drugs are poorly soluble in water at physiological pH. Id., 1:26-30. 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., 1:38-39.
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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., 3:4-9. 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., 3:9-10; Amiji Decl’n (EX. 1002), ¶ 20 (“[D]iclofenac’s
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`poor water solubility becomes the rate-limiting factor in its oral 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 ‘387 patent (EX. 1001), 1:63-65; 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 ‘387 patent (EX. 1001), 2:3-8. However, as the ‘387 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., 2:12-22.
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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., 1:49-62 and 2:23-64. 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., 1:43-48. 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
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`1 Lupin’s Answering Claim Constr. Br. (EX. 2001), p. 26.
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`active ingredient, including its particle size, will affect the dissolution
`profile.2
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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
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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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`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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`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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`III. THE ‘387 PATENT
`A. The ‘387 patent discloses diclofenac acid solid oral unit doses having
`improved dissolution profiles
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`
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`The ‘387 patent covers methods for treating pain by administering a solid
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`oral unit dose of a composition containing diclofenac acid, a poorly water-soluble
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`analgesic. The composition itself is formulated to have a certain particle size range
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`and a particular dissolution profile when tested in vitro according to a defined test
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`protocol. See, e.g., the ‘387 patent (EX. 1001), 54:62 to 55:49 (Example 14).
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`Improving the dissolution profile of diclofenac acid, and thus its bioavailability,
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`makes it possible to use lower doses of diclofenac relative to conventional
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`diclofenac formulations. Id., 39:4-7 (“The diclofenac compositions of the
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`invention preferably exhibit increased bioavailability (AUC) and require smaller
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`doses as compared to prior conventional compositions administered at the same
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`dose”). Lowering the dose minimizes the side effects of diclofenac acid, which
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`can include increased risk of gastrointestinal bleeding and cardiovascular side
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`effects. See Chuasuwan (EX. 1009), p. 1208; Amiji Decl’n (EX. 1002), ¶ 18.
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`The compositions disclosed in the ‘387 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 ‘387 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 dissolution profile, including the composition of the
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`drug itself (e.g., acid vs. salt), as well as the particular excipients included in a
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`solid oral unit dosage form of the drug (e.g., milling agents, surfactants, and the
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`like). See EXS. 2001, p. 26; 2002, p. 23, ¶ 82; and 2003, p. 11, 41:18 to 42:1.
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`C. The ‘387 patent relies on a test for measuring the dissolution profile
`of a given diclofenac acid solid oral unit dose
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`The ‘387 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 ‘387 patent (EX. 1001), 24:57-63.
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`The claims of the ‘387 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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`4 ‘387 patent, claim 1. Claim 11, the other independent claim, recites that at least
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`95%, by weight, is released by 75 minutes.
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`Example 14 of the ‘387 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 ‘387 patent (EX. 1001), 54:62 to
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`55:49. Even though salts were thought to be more soluble than acids, the test
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`results demonstrated that the ‘387 patent’s diclofenac acid tablet had an improved
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`dissolution profile relative to Novartis’ commercial diclofenac salt tablet. Id.,
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`55:18-33 (Table 14a).
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`Lupin acknowledges that the test protocol set forth in Example 14 and the
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`‘387 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. 18-21; 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 ‘387 patent claims
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`During prosecution, iCeutica filed a preliminary amendment that presented
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`application claims 72-99 for consideration. EX. 1027, pp. 285-89. The two
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`independent claims, application claims 72 and 85, recited treating pain by
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`administering a unit dose of a pharmaceutical composition containing either 18 mg
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`(claim 72) or 35 mg (claim 85) of diclofenac acid. Id., pp. 286-87. Dependent
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`claims 73 and 86, which depended on claims 72 and 85, respectively, required the
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`diclofenac acid to have a median particle size, on a volume average basis, of less
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`than 1000 nm and greater than 25 nm. Id., pp. 286-87. Dependent claims 74 and
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`87, which depended on claims 72 and 85, respectively, recited the dissolution
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`profile requirement currently found in issued independent claims 1 and 11. See id.,
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`pp. 286-87.
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`In an Office Action mailed June 24, 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. 299-302. 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 72 and 85 required. Id., p. 300. With respect to claims 73
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`and 86, 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 combined.
`Id., p. 301.
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`In response to the Office Action, iCeutica amended claims 72 and 85 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. 318-19. iCeutica also added dependent claims 100
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`and 101, which depended on claims 72 and 85, respectively, and recited the
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`dissolution profile requirements found in dependent application claims 74 and 87.
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`Id., pp. 318-21. Claims 100 and 101 correspond to issued patent claims 1 and 11,
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`respectively, and recite both a particle size range and dissolution properties.
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`iCeutica also argued that the pending claims were not obvious over Meiser plus
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`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. 323.
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`The Examiner continued to reject the claims. However, in an Office Action
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`
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`mailed January 15, 2015, he stated that claims 100 and 101, which recited specific
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`dissolution profiles, would be allowable on the ground that these claims were
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`commensurate with the unexpected results iCeutica had presented:
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`The method of claims 100 and 101 is patentable over the cited prior
`art since the method 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. 363.
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`
`
`
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`Claims 100 and 101 issued as patent claims 1 and 11, respectively.
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`The Examiner’s decision to allow claims 100 and 101, which required a
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`particular dissolution profile, while continuing to reject claims that recited only a
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`certain particle size range, demonstrate he recognized that particle size alone did
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`not determine dissolution profile. On the contrary, as Lupin and Dr. Amiji have
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`admitted, 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).
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`Claim 1 reads as follows (paragraph structure added for clarity):
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`1. A method for treating pain comprising administering 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.
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`Independent claim 11 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.
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`Pharmacopoeia at 100 rpm, at 37ºC. in 900 ml of 0.05% sodium lauryl sulfate in
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`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
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`according to their ordinary and customary meaning.
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`A. The dissolution profile is entitled to patentable weight
`The dissolution profile defines the diclofenac acid-containing solid oral unit
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`dose functionally in terms of its dissolution properties measured under certain test
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`conditions identified in the claims. Specifically, it requires the diclofenac acid-
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`containing solid oral unit dose to release a certain amount of diclofenac acid within
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`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 37º C. in 900 ml of 0.05% sodium lauryl sulfate
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`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
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`acid, by weight, by 75 minutes. In the case of independent claim 11, the diclofenac
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`acid-containing solid oral unit dose must release at least 95% diclofenac acid, by
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`weight, by 75 minutes.
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`The broadest reasonable interpretation of the ‘387 patent’s method of
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`treatment claims is that the dissolution profile affirmatively limits the claims by
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`defining the diclofenac acid-containing solid oral unit doses that are administered
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`for treating pain. The dissolution profile, therefore, is entitled to patentable
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`weight. It cannot be ignored, as Lupin urges. See Hoffer v. Microsoft Corp., 405
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`F.3d 1326, 1329 (Fed. Cir