`
`
`Filed: December 28, 2015
`
`Filed on behalf of Petitioners,
`Lupin Limited and Lupin Pharmaceuticals, Inc.
`By: Christy G. Lea
`
`Kerry S. Taylor
`
`Benjamin Anger
`
`KNOBBE, MARTENS, OLSON & BEAR, LLP
`2040 Main Street, 14th Floor
`
`
`Irvine, CA 92614
`
`Tel.: (949) 760-0404
`
`Fax: (949) 760-9502
`
`Email: BoxLupin15B@knobbe.com
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________________________
`
`LUPIN LIMITED
`AND LUPIN PHARMACEUTICALS. INC.,
`Petitioners
`
`v.
`iCEUTICA PTY LTD.
`
`Patent Owner
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Case No. TBD
`U.S. Patent No. 9,017,721
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,017,721
`
`
`
`TABLE OF CONTENTS
`
`Page No.
`
`I. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(1) ....................... 1
`A.
`Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1) .......................... 1
`
`Related Matters Under 37 C.F.R. § 42.8(b)(2) ................................... 1
`B.
`Lead and Back-up Counsel Under 37 C.F.R. § 42.8(b)(3) ................. 2
`C.
`Service Information Under 37 C.F.R. § 42.8(b)(4) ............................. 2
`D.
`Grounds for Standing Under 37 C.F.R. § 42.104(a) ........................... 3
`E.
`SUMMARY OF THE ISSUE PRESENTED ................................................ 3
`II.
`III. BACKGROUND AND STATE OF THE ART ............................................ 4
`A. Diclofenac Is a Well-Known NSAID ................................................. 4
`Skilled Artisans Knew to Reduce the Dose and Improve
`B.
`Bioavailability of Diclofenac .............................................................. 5
`iCeutica’s Payne Application Disclosed Nanosized
`Diclofenac Acid ................................................................................... 7
`iCeutica’s Meiser Application Disclosed Nanosized
`Diclofenac Acid ................................................................................... 8
`IV. THE ’721 PATENT ....................................................................................... 9
`The ’721 Patent Copies from Patent Owner’s Own Prior Art
`A.
`Publications, Meiser and Payne ........................................................ 10
`The ’721 Patent Mentions Payne and Meiser, But Only in
`Passing ............................................................................................... 12
`The ’721 Patent Teaches, But Does Not Claim,
`“Commercial Scale” Milling ............................................................. 12
`
`C.
`
`D.
`
`B.
`
`C.
`
`- i -
`
`
`
`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`D.
`
`Example 14 of the ’721 Patent .......................................................... 14
`1.
`The FDA Requires Dissolution Data ...................................... 16
`
`V.
`
`B.
`
`C.
`
`The Dissolution Test Conditions Came From the
`USP and FDA .......................................................................... 17
`The Prosecution History of the ’721 Patent ...................................... 21
`E.
`THE IROKO AND ICEUTICA ADMISSIONS ......................................... 24
`The Iroko Prospectus Admits that Meiser Discloses
`A.
`iCeutica’s Diclofenac Product .......................................................... 24
`iCeutica’s Press Release Admits Cammarano Covers
`iCeutica’s Method of Making Zorvolex ............................................ 27
`Cammarano’s Claims Are Further Evidence that the ’721
`Patent Adds Only a Dissolution Test ................................................ 29
`VI. LEVEL OF ORDINARY SKILL IN THE ART ......................................... 30
`VII. CONSTRUCTION OF THE CHALLENGED CLAIMS ........................... 30
`“Wherein . . . When Tested” Clauses Deserve No
`A.
`Patentable Weight .............................................................................. 32
`“Wherein . . . When Tested” Clauses Do Not Add
`1.
`Substance to the Claims .......................................................... 32
`The Dissolution Testing Is an Optional Condition in
`the Claims ............................................................................... 35
`VIII. SPECIFIC GROUNDS FOR CANCELLATION OF
`CLAIMS 1-24 .............................................................................................. 36
`
`2.
`
`2.
`
`- ii -
`
`
`
`TABLE OF CONTENTS
`(cont’d)
`
`Page No.
`
`The Grounds of Rejection Are Not Redundant ................................. 37
`A.
`B. Ground 1: Claims 1-24 Would Have Been Obvious Over
`Meiser in View of the Novartis Package Insert ................................ 37
`1.
`Claims 1 and 8 ......................................................................... 38
`2.
`Claims 2-7 and 9-24 ................................................................ 44
`C. Ground 2: Claims 1-24 Would Have Been Obvious Over
`Meiser in View of the Novartis Package Insert, and in
`Further View of the USP and Chuasuwan ........................................ 47
`1.
`Claims 1 and 8 ......................................................................... 50
`2.
`Claims 3-5 and 10-12 .............................................................. 55
`3.
`Claims 2, 6-7, 9, and 13-24 ..................................................... 56
`D. Ground 3: Claims 1-24 Would Have Been Obvious Over
`Meiser in View of the Novartis Package Insert, in View of
`the USP and Chuasuwan, and Further in View of Reiner ................. 57
`IX. SECONDARY CONSIDERATIONS, EVEN IF PRESENT, FAIL
`TO OVERCOME THE STRONG EVIDENCE OF
`OBVIOUSNESS .......................................................................................... 58
`CONCLUSION ............................................................................................ 60
`
`X.
`
`- iii -
`
`
`
`TABLE OF AUTHORITIES
`
`Page No(s).
`
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) ...................................................................... 40, 49
`
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) .......................................................................... 39
`
`Ex Parte Berzofsky,
`Appeal No. 1010-011270, 2011 WL 891756
`(B.P.A.I. Mar. 10, 2011) ..................................................................................... 34
`
`In re Cuozzo Speed Techs., LLC,
`793 F.3d 1268 (Fed. Cir. 2015) .......................................................................... 31
`
`In re Droge,
`695 F.3d 1334 (Fed. Cir. 2012) .......................................................................... 59
`
`In re Geisler,
`116 F.3d 1465 (Fed. Cir. 1997) .......................................................................... 41
`
`Hoffer v. Microsoft Corp.,
`405 F.3d 1326 (Fed. Cir. 2005) .................................................................... 33, 34
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 36, 49
`
`In re Kulling,
`897 F.2d 1147 (Fed. Cir. 1990) .......................................................................... 41
`
`Minton v. Nat’l Ass’n of Securities Dealers, Inc.,
`336 F.3d 1373 (Fed. Cir. 2003) .............................................................. 33, 34, 35
`
`Not Dead Yet Mfg., Inc. v. Pride Sols., LLC,
`No. 13 C 3418, 2015 WL 5829761 (N.D. Ill. Oct. 5, 2015) ......................... 34, 35
`
`Par Pharm., Inc. v. TWi Pharms., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) .............................................................. 49, 50, 55
`
`- iv -
`
`
`
`TABLE OF AUTHORITIES
`(cont’d)
`
`Page No(s).
`
`In re Paulsen,
`30 F.3d 1475 (Fed. Cir. 1994) ............................................................................ 32
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .......................................................................... 40
`
`Renishaw PLC v. Marposs Societa’ per Azioni,
`158 F.3d 1243 (Fed. Cir. 1998) .......................................................................... 36
`
`Richardson-Vicks Inc. v. Upjohn,
`122 F.3d 1476 (Fed. Cir. 1997) .......................................................................... 59
`
`Santarus Inc. v. Par Pharm. Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) .................................................................... 50, 55
`
`SIBIA Neurosciences Inc. v. Cadus Pharm. Corp.,
`225 F.3d 1349 (Fed. Cir. 2000) .......................................................................... 58
`
`Texas Instruments Inc. v. U.S. Int’l Trade Comm’n,
`988 F.2d 1165 (Fed. Cir. 1993) .......................................................................... 32
`
`In re Translogic Tech., Inc.,
`504 F.3d 1249 (Fed. Cir. 2007) .................................................................... 31, 32
`
`OTHER AUTHORITIES
`
`21 C.F.R. § 314.53 ................................................................................................... 27
`
`35 U.S.C. § 102 .................................................................................................passim
`
`35 U.S.C. §§ 311-319 ................................................................................................ 1
`
`37 C.F.R. § 42.15 ..................................................................................................... 60
`
`37 C.F.R. § 42.100 ............................................................................................... 1, 31
`
`- v -
`
`
`
`TABLE OF AUTHORITIES
`(cont’d)
`
`Page No(s).
`
`37 C.F.R. § 42.104 ..................................................................................................... 3
`
`MPEP § 2111.04 ...................................................................................................... 32
`
`
`
`
`- vi -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`EXHIBIT LIST
`
`Description
`
`Exhibit
`No.
`1001 U.S. Patent No. 9,017,721
`
`1002 Declaration of Mansoor Amiji, Ph.D.
`
`1003 Curriculum Vitae of Mansoor Amiji, Ph.D.
`
`1004
`
`1005
`
`Short
`Citation
`’721 patent
`
`
`
`
`
`
`
`List of documents reviewed by Mansoor Amiji, Ph.D.
`in preparation of his declaration
`
`PCT Publication No. WO2008/000042, published
`January 3, 2008
`
`Meiser
`
`1006 Novartis Package Insert for Cataflam®, Voltaren®,
`and Voltaren®-XR, dated May 2000
`
`Novartis
`Package Insert
`
`1007 United States Pharmacopeia 30, Section <711> (2007) USP <711>
`
`1008 United States Pharmacopeia 30, Section <1092>
`(2007)
`
`1009 Chuasuwan et al., “Biowaiver Monographs for
`Immediate Release Solid Oral Dosage Forms
`Diclofenac Sodium and Diclofenac Potassium,”
`98(4):1206-1219 (2009)
`
`USP <1092>
`
`Chuasuwan
`
`1010
`
`1011
`
`PCT Publication No. WO2006/133954, published
`December 21, 2006
`
`Reiner
`
`PCT Publication No. WO2006/069419, published July
`6, 2006
`
`Payne
`
`Exhibit List, Page 1
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`Description
`
`Exhibit
`No.
`1012 Moore, “Diclofenac Potassium 12.5mg Tablets for
`Mild to Moderate Pain and Fever: A Review of Its
`Pharmacology, Clinical Efficacy and Safety,”
`27(3):163-195 (2007)
`
`Short
`Citation
`Moore
`
`1013 U.S. Patent No. 5,256,699 to Murphy et al.
`
`
`
`1014 Dokoumetzidis et al., “A century of dissolution
`research: From Noyes and Whitney to the
`Biopharmaceutics Classification System,” Int’l Journal
`of Pharmaceutics 321:1-11 (2006)
`
`Dokoumetzidis
`
`1015 Kesisoglou et al., “Nanosizing – Oral Formulation
`Development and Biopharmaceutical Evaluation,”
`Advanced Drug Delivery Reviews, 59:631-644 (2007)
`
`Kesisoglou
`
`1016 U.S. Patent No. 5,202,129 to Samejima et al.
`
`1017 U.S. Patent Publication 2006/0159628 to Liversidge
`
`1018 Vogt et al., “Dissolution enhancement of Fenofibrate
`by Micronization, Cogrinding and Spray-drying:
`Comparison with Commercial Preparations,”
`European Journal of Pharmaceutics and
`Biopharmaceutics 68:283-288 (2008)
`
`Samejima
`
`Liversidge
`’628
`
`Vogt
`
`1019 U.S. Patent Publication 2006/0204588 to Liversidge et
`al.
`
`Liversidge
`’588
`
`1020 U.S. Patent No. 8,808,751 to Cammarano, et al.
`
`Cammarano
`
`1021
`
`Iroko F-1 Prospectus filed with the Securities and
`Exchange Commission on June 18, 2013
`
`Iroko
`Prospectus
`
`Exhibit List, Page 2
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`Description
`
`Exhibit
`No.
`1022 Khazaeinia et al., “A Comparison of Gastrointestinal
`Permeability Induced by Diclofenac-phospholipid
`complex with Diclofenac Acid and its Sodium Salt,”
`Journal of Pharmaceutical Sciences 6(3):352-359
`(2003)
`
`Short
`Citation
`Khazaeinia
`
`1023
`
`iCeutica Press Release, “iCeutica Receives Key Patent
`for SoluMatrix Fine Particle Technology Platform”
`(September 24, 2014)
`
`iCeutica Press
`Release
`
`1024 Memorandum dated April 6, 2005, from John Jenkins,
`M.D., at FDA re: “Analysis and recommendations for
`Agency action regarding non-steroidal anti-
`inflammatory drugs and cardiovascular risk”
`
`1025 U.S. Dep’t of Health & Human Servs., Food and
`Drug Admin., CDER, Guidance for Indus.,
`Dissolution Testing of Immediate Release Solid Oral
`Dosage Forms (1997)
`
`Jenkins Memo
`
`FDA Guidance
`
`1026 Royal Hanson et al. Handbook of Dissolution Testing
`1-53 (3rd ed. 2004)
`
`Handbook
`
`1027
`
`’721 Patent Reduced File History
`
`File History
`
`1028
`
`1029
`
`iCeutica Press Release dated April 28, 2011: iCeutica
`Announces Sale to Partner Iroko; 10X uplift on
`original value
`
`FDA Orangebook listing for Zorvolex; available at:
`http://www.accessdata.fda.gov/scripts/cder/ob/docs
`/obdetail.cfm?Appl_No=204592&TABLE1=OB_Rx;
`and
`http://www.accessdata.fda.gov/scripts/cder/ob/docs /
`/patexclnew.cfm?Appl_No=204592&Product_No=001
`&table1=OB_Rx (accessed November 2, 2015)
`
`
`
`
`
`Exhibit List, Page 3
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`Exhibit
`No.
`1030
`
`Description
`
`Loewenstein and Roberts “The Ionization of Citric
`Acid Studied by the Nuclear Magnetic Resonance
`Technique” J. of Am. Chem. Soc. 82(11) 2705-2710
`(1960)
`
`Short
`Citation
`
`
`1031 Rune and Viskum, “Duodenal pH values in normal
`controls and in patients with duodenal ulcer,” Gut
`10:569-571 (1969)
`
`1032 Countdown to the 10th Anniversary Scrip Awards,
`available at: https://ibiawards.com/scrip-awards/wp-
`content/uploads/sites/41/2014/11/script_shottlist_ad6_
`141125_16.pdf (accessed November 2, 2015)
`
`1033 U.S. Patent No. 3,558,690
`
`1034 United States Pharmacopeia 30, Official Monographs
`for Diclofenac Potassium and Diclofenac sodium, pp.
`1921-1924 (2007)
`
`1035 Remington’s Pharmaceutical Handbook Excerpt, 18th
`ed., pp. 715-716 (1990)
`
`1036 HPPS Operators Guide, Malvern Instruments, 2.0
`(2003)
`
`1037 U.S. Provisional Application No. 61/172,291
`
`1038 Australian Provisional Application No. 2009901748
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Exhibit List, Page 4
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`Petitioners Lupin Limited and Lupin Pharmaceuticals, Inc. (“Lupin” or
`
`“Petitioners”) request inter partes review in accordance with 35 U.S.C. §§ 311-319
`
`and 37 C.F.R. § 42.100 et seq. of claims 1-24 of U.S. Pat. No. 9,017,721 (“the ’721
`
`patent”) which issued on April 28, 2015 and is owned by iCeutica Pty Ltd.
`
`(“iCeutica” or “Patent Owner”).
`
`I.
`
`MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(A)(1)
`
`The following mandatory notices are provided as part of this Petition.
`
`A. Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1)
`Lupin Limited and Lupin Pharmaceuticals, Inc. are the real parties-in-
`
`interest.
`
`B. Related Matters Under 37 C.F.R. § 42.8(b)(2)
`The ’721 patent has been asserted in a co-pending litigation captioned
`
`iCeutica Pty Ltd and Iroko Pharmaceuticals, LLC v. Lupin Limited and Lupin
`
`Pharmaceuticals, Inc., No. 1:14-cv-01515-SLR-SRF (D. Del., filed December 23,
`
`2014). Petitioners are parties to that litigation. iCeutica and Iroko Pharmaceuticals,
`
`LLC (“Iroko”) (collectively, “Plaintiffs”) served their original Complaint on Lupin
`
`on December 29, 2014. The initial complaint alleged infringement of one patent:
`
`U.S. Patent No. 8,679,544 (“the ’544 patent”). Plaintiffs served a First Amended
`
`Complaint on May 26, 2015, alleging infringement of the ’721 patent and U.S.
`
`Patent No. 8,999,387 (“the ’387 patent”). Concurrent with the filing of this
`
`- 1 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`Petition, Petitioners have filed a related petition requesting inter partes review of
`
`the ’387 patent. The ’544, ’387, ’721 patents list the same inventors and share a
`
`common specification.
`
`C. Lead and Back-up Counsel Under 37 C.F.R. § 42.8(b)(3)
`Lupin provides the following designation of counsel, all of whom are
`
`included in Customer No. 20,995 identified in Lupin’s Power of Attorney.
`
`Lead Counsel
`Christy G. Lea (Reg. No. 51,754)
`Knobbe, Martens, Olson & Bear, LLP
`2cgl@knobbe.com
`Postal and Hand-Delivery Address:
`2040 Main St., 14th Floor
`Irvine, CA 92614
`Telephone: (949) 760-0404
`Facsimile: (949) 760-9502
`
`First Back-up Counsel
`Kerry Taylor (Reg. No. 43,947)
`Knobbe, Martens, Olson, & Bear, LLP
`2kst@knobbe.com
`Postal and Hand-Delivery Address:
`12790 El Camino Real
`San Diego, CA 92130
`Telephone: (858) 707-4000
`Facsimile:
`(858) 707-4001
`Second Back-up Counsel
`Benjamin Anger (Reg. No. 62,207)
`Knobbe, Martens, Olson, & Bear, LLP
`2bba@knobbe.com
`Postal and Hand-Delivery Address:
`12790 El Camino Real
`San Diego, CA 92130
`Telephone: (858) 707-4000
`Facsimile:
`(858) 707-4001
`
`Service Information Under 37 C.F.R. § 42.8(b)(4)
`
`D.
`Please address all correspondence to lead counsel and back-up counsel at the
`
`addresses shown above. Petitioners also consent to electronic service by email to:
`
`BoxLupin15B@knobbe.com.
`
`- 2 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`E. Grounds for Standing Under 37 C.F.R. § 42.104(a)
`Petitioners certify that the ’721 patent is available for inter partes review
`
`and that Petitioners are not barred or estopped from requesting an inter partes
`
`review challenging the patent claims on the grounds identified in this Petition.
`
`This Petition is being filed within one year of service of Plaintiffs’ First Amended
`
`Complaint against Petitioners in the district court litigation referenced above.
`
`II.
`
`SUMMARY OF THE ISSUE PRESENTED
`
`iCeutica’s claimed diclofenac product was disclosed in an earlier iCeutica
`
`patent application, the Meiser PCT application. iCeutica has repeatedly admitted
`
`this fact. Meiser was before the Examiner during prosecution of the ’721 patent.
`
`The Examiner, however, misunderstood the extent of Meiser’s disclosure and did
`
`not have the benefit of iCeutica’s admissions regarding Meiser.
`
`The ’721 patent differs from Meiser only in so far as it discloses a run-of-
`
`the-mill dissolution test and commercial-scale dry milling of diclofenac. Claims 1
`
`and 8 include a portion of the dissolution test, but no claim recites commercial-
`
`scale dry milling, which the inventors define as the invention of the ’721 patent. As
`
`a legal matter, the dissolution test should not be afforded patentable weight, as it
`
`does not provide any substance to the claimed method of administering diclofenac
`
`acid. As a factual matter, the dissolution rate is an inherent property of the
`
`- 3 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`diclofenac acid disclosed in Meiser. Even if given patentable weight, the recited
`
`dissolution test would have been obvious to a skilled artisan because it is based on
`
`the exact conditions recommended by the prior art, including the United States
`
`Pharmacopeia and FDA guidelines. Thus, the dissolution test conditions were the
`
`obvious choice, and the measured dissolution rates were a matter of routine
`
`optimization, and a natural result of the test conditions.
`
`III.
`
`BACKGROUND AND STATE OF THE ART
`
`The independent claims of the ’721 patent relate to a solid oral unit dose of
`
`diclofenac acid, wherein (1) the unit dose contains 18 mg (or 35 mg) of diclofenac
`
`acid; and (2) the diclofenac acid has a median particle size between 1000 nm and
`
`25 nm. The independent claims also include a clause stating that the unit dose,
`
`when tested in vitro via a standard test method, has a dissolution rate characterized
`
`by 94% (or 95%) of the diclofenac acid being released by 75 minutes.
`
`A. Diclofenac Is a Well-Known NSAID
`Diclofenac is a well-known drug, and part of the class of drugs known as
`
`non-steroidal anti-inflammatory drugs, or NSAIDs. Declaration of Dr. Mansoor
`
`Amiji, Ph.D, R.Ph., Ex. 1002, ¶ 15. Diclofenac has been used for decades as an
`
`analgesic
`
`to
`
`treat both chronic and acute pain. Id.; PCT Publication
`
`WO2006/133954 to Reiner (“Reiner”), Ex. 1010 at 1.
`
`- 4 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`B.
`
`Skilled Artisans Knew to Reduce the Dose and Improve
`Bioavailability of Diclofenac
`
`As with other NSAIDs, one of ordinary skill generally understood
`
`diclofenac’s analgesic properties to come from its inhibition of cyclooxegenase
`
`(COX) enzymes, known as COX-1 and COX-2. Ex. 1002, ¶ 17; Moore, Ex. 1012
`
`at 165. Like other COX-inhibiting NSAIDs, diclofenac has been associated with an
`
`increased risk of gastrointestinal bleeding and serious cardiovascular side effects.
`
`Ex. 1002, ¶ 18; Chuasuwan, Ex. 1009 at 1208.
`
`In 2004, the NSAID rofecoxib (Vioxx®) was pulled from the market due to
`
`elevated risk of cardiovascular incidents. Ex. 1012 at 188. In 2005, in the wake of
`
`the Vioxx® withdrawal and general concerns over NSAIDs,
`
`the FDA
`
`recommended that all NSAIDs remaining on the market be prescribed at the lowest
`
`effective dose for the shortest possible duration. Jenkins Memo, Ex. 1024 at 15.
`
`Thus, one of ordinary skill knew at the time of the ’721 patent that reducing the
`
`required dose of NSAIDs, such as diclofenac, would reduce the known negative
`
`side-effects of NSAIDs.
`
`
`
`One of ordinary skill also knew that diclofenac acid exhibits poor water
`
`solubility, leading to low oral bioavailability. Ex. 1002, ¶¶ 20, 29; Ex. 1009 at
`
`1214. By 1993, those of ordinary skill recognized that a drug with low water
`
`solubility “often shows insufficient bioavailability because of the poor solubility in
`
`- 5 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`gastrointestinal fluids, which compels said drug to pass through the site of
`
`absorption before it completely dissolves in the fluids.” U.S. Patent No. 5,202,129
`
`to Samejima, Ex. 1016 at 1:19-24. Samejima describes methods to improve
`
`bioavailability of poorly water soluble drugs, including formulating water-soluble
`
`salts, soft gelatin capsules containing a solution of said drug in a nonaqueous
`
`solvent, and adsorbing the drug onto porous materials. Id. at 1:29-44. Per
`
`Samejima, these methods each suffer from drawbacks, including altering
`
`pharmaceutical activity of a drug (as is the case with salts) and difficulty of finding
`
`acceptable nonaqueous solvents.
`
`
`
`Samejima also addresses poor solubility by reducing drug particle size
`
`through milling. Specifically, Samejima teaches milling naproxene (an NSAID
`
`marketed in the U.S. as Aleve) to “preferably less than 1 μm” to improve
`
`dissolution and water solubility. Id. at 2:43-49, 4:14-45.
`
`A skilled artisan well knew the relationship between lowering particle size
`
`and increasing dissolution rate. In 2007, Kesisoglou et al., using the Nernst-
`
`Brunner/Noyes-Whitney equation, explained that “nanosizing,” or “the reduction
`
`of the active pharmaceutical ingredient (API) particle size down to the sub-micron
`
`range,” would improve dissolution of a drug. Ex. 1015 at 632; see also Ex. 1002,
`
`¶¶ 27-28. Kesisoglou stated that particle size reduction had been employed in the
`
`- 6 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`pharmaceutical industry for decades, but “recent advances in milling technology
`
`and our understanding of such colloidal systems have enabled the production of
`
`API particles of 100-200 nm size in a reproducible manner. . . . These
`
`nanoformulations offer increased dissolution rates for drug compounds and
`
`complement other technologies used to enhance bioavailability of insoluble
`
`compounds (BCS Class II and IV) such as solubility enhancers (i.e.
`
`surfactants). . . . ” Ex. 1015 at 632; see also Ex. 1002, ¶ 29.
`
`Thus, one of ordinary skill knew that reducing the particle size of a drug
`
`would increase the drug’s surface area, which in turn would increase the drug’s
`
`exposure to the solvent, thereby increasing the drug’s solubility. Ex. 1002, ¶¶ 27-
`
`29. Reducing particle size to improve dissolution and bioavailability has been
`
`effective for many other drugs, including raloxifene, fenofibrate, finasteride,
`
`dustasteride, and
`
`tamsulosin. See Ex. 1017, ¶¶ [0034]-[0037] (teaching
`
`nanoparticulate raloxifene hydrochloride); Ex. 1018 at 283 (teaching nanosizing
`
`fenofibrate); and Ex. 1019, ¶ [0042] (teaching nanoparticulate finasteride,
`
`dutasteride, and tamsulosin); see also Ex. 1002, ¶¶ 26, 30-32.
`
`iCeutica’s Payne Application Disclosed Nanosized Diclofenac Acid
`
`C.
`iCeutica, the owner of the ’721 patent, filed its first patent application
`
`directed to nanosizing diclofenac acid in 2005 (Payne) and its second in 2007
`
`- 7 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`(Meiser). iCeutica filed PCT Application No. PCT/AU2005/001977 on December
`
`30, 2005. It published as WO2006/069419 (Ex. 1011, “Payne”) on July 6, 2006;
`
`Thus, Payne qualifies as prior art to the ’721 patent under pre-AIA 35 U.S.C. §
`
`102(b).
`
`Payne described forming nanoparticle compositions and “a method for
`
`preparing said compositions and preparations using solid-state mechanochemical
`
`synthesis.” Ex. 1011 at 1:6-10. Payne demonstrates that skilled artisans, and
`
`iCeutica itself, recognized the value of nanosizing diclofenac acid to improve
`
`solubility and bioavailability; Payne taught: “It is known that the rate of dissolution
`
`of a particulate drug can increase with increasing surface area, that is, decreasing
`
`particle size.” Id. at 1:25-26. Payne also described improving dissolution of
`
`diclofenac acid, using milling techniques to create diclofenac nanoparticles having
`
`an average size less than 200 nm. Id. at 1:25-26, 17:1-4, 26 Table 1, 42:9-43:26,
`
`Claim 36; Ex. 1002, ¶ 33.
`
`D.
`
`iCeutica’s Meiser Application Disclosed Nanosized Diclofenac
`Acid
`
`iCeutica filed International Patent Application No. PCT/AU2007/000910 on
`
`June 29, 2007. It published as WO2008/000042 (Ex. 1005, “Meiser”) on January 3,
`
`2008; therefore Meiser qualifies as prior art to the ’721 patent under pre-AIA 35
`
`U.S.C. § 102(b).
`
`- 8 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`Meiser’s Background Section is nearly identical to that of Payne and taught
`
`improving the solubility of diclofenac acid by dry milling to obtain nanoparticles.
`
`Ex. 1005 at, e.g., 6-7, 27-28. Meiser states, “biologically active compounds that are
`
`poorly water soluble at physiological pH will particularly benefit from being
`
`prepared in nanoparticulate form.” Ex. 1005 at 27. Meiser identified diclofenac
`
`acid as a poorly water soluble compound for which the nanosizing methods were
`
`suitable. Id. at 28. Thus, improving bioavailability of diclofenac acid by forming
`
`nanoparticles was well known in the prior art.
`
`Meiser also teaches that drugs in nanoparticulate form have advantages over
`
`conventional compounds: more rapid therapeutic action and achieving a given
`
`therapeutic effect with a lower dose. Ex. 1005 at 7. Thus, lowering the dose by
`
`using nanoparticles was well known in the prior art. It was also well known that
`
`lowering the dose would reduce negative gastrointestinal and cardiovascular side
`
`effects of NSAIDs, such as diclofenac. Ex. 1024 at 15.
`
`IV.
`
`THE ’721 PATENT
`
`iCeutica filed the ’721 patent on May 14, 2014 as a continuation of U.S.
`
`Patent Application No. 13/266,122 (now U.S. Patent No. 8,735,450 (“the ’450
`
`patent”)), which was a national phase entry of International Patent Application No.
`
`PCT/AU2010/000471, filed on April 23, 2010. This PCT application claims
`
`- 9 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`priority to U.S. Provisional Application No. 61/172,291 (Ex. 1037), and to
`
`Australian Provisional Application No. 2009901748 (Ex. 1038), both filed on April
`
`24, 2009. Thus, April 24, 2009 is the earliest possible priority date for the ’721
`
`patent. However, the specification of the ’721 patent includes disclosure not
`
`present in either the Australian or U.S. provisional applications, including the
`
`dissolution testing described in Example 14 of the ’721 patent. Thus, the earliest
`
`possible priority date for the dissolution testing subject matter in Claims 1 and 8 is
`
`the filing date of the PCT application, April 23, 2010.
`
`A. The ’721 Patent Copies from Patent Owner’s Own Prior Art
`Publications, Meiser and Payne
`
`The ’721 patent addresses the same solubility and bioavailability issues that
`
`Payne and Meiser addressed. The ’721 patent copies large portions of Payne’s and
`
`Meiser’s Background sections verbatim. Ex. 1002, ¶ 59.
`
`The ’721 patent restates Payne’s and Meiser’s descriptions regarding
`
`bioavailability of drugs having poor water solubility. For example, both Payne and
`
`Meiser state that “[p]oor bioavailability is a significant problem encountered in the
`
`development of therapeutic compositions, particularly those compounds containing
`
`a biologically active compound that is poorly soluble in water at physiological
`
`pH.” Ex. 1005 at 1; Ex. 1011 at 1. The ’721 patent contains nearly identical
`
`language at 1:26-30.
`
`- 10 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
`The ’721 patent restates Payne’s and Meiser’s discussion regarding the
`
`relationship between particle size, dissolution rate, and bioavailability. Payne and
`
`Meiser both describe that dissolution rate affects bioavailability, and that “[i]t is
`
`known that the rate of dissolution of a particulate drug will increase with
`
`increasing surface area.” Ex. 1005 at 1; Ex. 1011 at 1. This verbatim language
`
`appears in the ’721 patent at 1:43-45.
`
`The ’721 patent also restates Payne’s and Meiser’s argument that
`
`conventional dry milling techniques could only yield particle sizes in the 100
`
`micron (100,000 nm) range and that wet milling techniques can produce particles
`
`only in the 10 micron (10,000 nm) range. Ex. 1005 at 2; Ex. 1011 at 1-2; cf. ’721
`
`patent, Ex. 1001 at 1:51-59. This is noteworthy, as the ’721 patent does not even
`
`acknowledge Payne’s and Meiser’s disclosures that their milling techniques
`
`achieve particles sizes less than 1,000 nm. Instead, the ’721 patent brazenly states:
`
`“In one surprising aspect the particle size produced by the [dry milling] process is
`
`equal to or less than 2000 nm. In another surprising aspect the particle size
`
`produced by the process is equal to or less than 1000 nm.” Ex. 1001 at 3:60-62; see
`
`also Ex. 1002, ¶ 61. Of course, this was not surprising; the prior art Payne and
`
`Meiser references already disclosed this.
`
`- 11 -
`
`
`
`Lupin v. iCeutica Pty Ltd
`IPR re U.S. Patent 9,017,721
`
` The ’721 Patent Mentions Payne and Meiser, But Only in Passing
`
`B.
`The ’721 patent mentions Payne and Meiser, but attempts to minimize their
`
`relevance. The ’721 patent describes Payne as merely disclosing a mechano-
`
`chemical synthesis process of milling active particles in a carrier matrix. Ex. 1001
`
`at 2:43-59. Of Meiser, the ’721 patent states that it “describes, inter alia, a method
`
`for dry milling raloxifene with lactose and NaCl which produced nanoparticulate
`
`raloxifene without significant aggregation problems.” Ex. 1001 at 2:62-65. The
`
`’721 patent does not acknowledge Payne’s or Meiser’s disclosures that they first
`
`achieved particle sizes less than 1000 nm for diclofenac acid. Instead, the ’721
`
`patent relegates Meiser’s critical teaching regarding nanoparticulate diclofenac
`
`acid to the catch-all phrase “inter alia,” stating only that Meiser “describes, inter
`
`alia, a method for dry milling raloxifene . . . .” Id. (emphasis added).
`
`C. The ’721 Patent Teaches, But Does Not Claim, “Commercial
`Scale” Milling
`
`The ’721 patent purports to have invented a “commercial-scale” milling
`
`method. See Ex. 1001 at 2:66-3:4. The ’721 patent states: “The present invention is
`
`directed to the unexpected finding that particles of a biologically active material
`
`can be produced by dry milling processes as described herein at commercial scale”
`
`resulting in “a more efficient and cost effective process.” Ex. 1001 at 24:26-33
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
