Petition for Inter Partes Review
`United States Patent No. 9,555,027
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`In re Inter Partes Review of:
`U.S. Patent No. 9,555,027
`Issued: January 31, 2017
`Application No.: 14/512,189
`Filing Date: Oct. 10, 2014
`
`For: Pharmaceutical Composition
`
`FILED VIA E2E
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`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 9,555,027
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`
`
`I.
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`
`II.
`
`
`TABLE OF CONTENTS
`
`Overview .......................................................................................................... 1
`
`Identification of Claims Being Challenged (37 C.F.R. § 42.104(B)) ............. 7
`
`
`
` Overview of the ’027 Patent ............................................................................ 8 III.
`
`A.
`B.
`
`Specification .......................................................................................... 8
`The ’027 Patent Claims Oral Preparations Comprising 20%-
`45% Lurasidone and 10%-50% Pregelatinized Starch ......................... 8
`
`
`
` The Person of Ordinary Skill in the Art .......................................................... 9 IV.
`
`V.
`
`
`Claim Construction ........................................................................................ 10
`
`A. Applicable Law ................................................................................... 10
`B.
`Construction of Claim Terms .............................................................. 10
`1.
`“equivalent dissolution profile” ................................................ 11
`2.
`“pregelatinized starch” .............................................................. 12
`
`
`
` Background and State of the Art ................................................................... 13 VI.
`
`A.
`
`B.
`C.
`
`Formulation of Oral Preparations with Good Disintegration and
`Rapid Dissolution Was Well-Known in the Art ................................. 13
`Formulations of Lurasidone Were Known .......................................... 15
`Pregelatinized Starch Was a Commonly-Used Disintegrant in
`Oral Dosage Forms .............................................................................. 16
`
`
`
` Scope and Content of the Prior Art ............................................................... 18 VII.
`
`A.
`
`B.
`
`C.
`
`Fujihara Disclosed Oral Preparations of Lurasidone Including
`Disintegrants ........................................................................................ 18
`Aulton Disclosed a Small Group of Common Disintegrants,
`Including Pregelatinized Starch .......................................................... 19
`Denton Disclosed Oral Preparations of a Poorly Soluble Drug
`Containing Pregelatinized Starch that Had High Drug Loads,
`Rapid Dissolution, and Equivalent Dissolution Between
`Dosages................................................................................................ 21
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`D.
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`Chowdary Taught the Amount of Pregelatinized Starch to
`Include in a Formulation to Obtain Rapid Dissolution and
`Disintegration ...................................................................................... 22
`
`
`
` Claims 1-34 Would Have Been Obvious Over the Prior Art ........................ 24 VIII.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`2.
`
`3.
`
`4.
`
`A. Ground 1: Claims 1-34 Would Have Been Obvious Over
`Fujihara in View of Aulton ................................................................. 24
`1.
`One of Ordinary Skill Would Have Been Motivated to
`Use the Lurasidone Oral Preparations of Fujihara ................... 25
`Fujihara Discloses Ranges of Lurasidone Content and
`Excipients that Overlap with the Challenged Claims ............... 26
`One of Skill Was Motivated to Select a Known
`Disintegrant in Fujihara ............................................................ 28
`It Would Have Been Obvious to Combine Fujihara With
`Aulton to Select Pregelatinized Starch as the Disintegrant
`Because It Was in a Small Group of Commonly-Used
`Disintegrants ............................................................................. 29
`There Is No Evidence of Unexpected Results from the
`Claimed Ranges of Lurasidone or Pregelatinized Starch ......... 33
`Fujihara and Aulton Render Obvious Every Limitation of
`the Claims ................................................................................. 36
`Ground 2: Claims 1-34 Would Have Been Obvious Over
`Fujihara in View of Denton and Chowdary ........................................ 47
`1.
`One of Ordinary Skill Would Have Been Motivated to
`Use the Lurasidone Oral Preparations of Fujihara ................... 48
`Denton Disclosed the Use of Pregelatinized Starch in
`Oral Preparations to Produce Higher Dosages, Maintain
`Acceptable Tablet Size, and Obtain Equivalent
`Dissolution Profiles Across Dosages ........................................ 48
`Chowdary Disclosed the Preferred Range of 10%-20%
`Pregelatinized Starch ................................................................ 50
`Fujihara, Denton, and Chowdary Render Obvious Every
`Limitation of the Claims ........................................................... 51
`There Was a Reasonable Expectation of Success in Formulating
`Pregelatinized Starch with Lurasidone ................................................ 57
`1.
`Sumitomo Incorrectly Asserted that Highly Relevant Art
`Should Be Disregarded ............................................................. 58
`
`B.
`
`C.
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
`
`2.
`
`Sumitomo Incorrectly Asserted that Pregelatinized Starch
`Has an Unpredictable Effect on Dissolution............................. 60
`The Prior Art Did Not Teach Away From the Claimed Range of
`Pregelatinized Starch ........................................................................... 63
`
`
`
`D.
`
` The Office Has Not Previously Considered Substantially the Same IX.
`
`
`Art, Evidence, or Arguments ......................................................................... 66
`
`X.
`
`
`Secondary Considerations Do Not Overcome the Strong Evidence of
`Obviousness ................................................................................................... 68
`
`Commercial Success............................................................................ 69
`A.
`Long-Felt But Unmet Need or Failure of Others ................................ 70
`B.
`Industry Praise ..................................................................................... 70
`C.
`D. Unexpected Results ............................................................................. 70
`
`
`
` Conclusion ..................................................................................................... 71 XI.
`
`
`
` Requirements for Petition for Inter partes Review ....................................... 71 XII.
`
`A. Grounds for Standing (37 C.F.R. § 42.104(a)) ................................... 71
`B.
`Notice of Real Party-in-Interest (37 C.F.R. § 42.8(b)(1))................... 71
`C.
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) ............................ 71
`D. Notice of Lead and Back-up Counsel and Service Information ......... 72
`Fee for Inter Partes Review ................................................................ 72
`E.
`F.
`Proof of Service ................................................................................... 72
`
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
`
`TABLE OF AUTHORITIES
`
`CASES
`
`10x Genomics v. Univ. of Chicago,
`IPR2015-01157, Paper 14 (Nov. 16, 2015) ..........................................................68
`
`Agrizap, Inc. v. Woodstream Corp.,
`520 F.3d 1337 (Fed. Cir. 2008) .............................................................................68
`
`Aventis Pharma S.A. v. Hospira, Inc.,
`743 F. Supp. 2d 305 (D. Del. 2010),
`aff’d, 675 F.3d 1324 (Fed. Cir. 2012) ................................................ 44, 59, 60, 70
`
`Coalition for Affordable Drugs II LLC v. NPS Pharms., Inc.,
`IPR2015-00990, Paper 28 (Oct. 23, 2015) ...........................................................68
`
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) .............................................................................44
`
`In re Geisler,
`116 F.3d 1465 (Fed. Cir. 1997) .............................................................................44
`
`Kayak Software Corp. v. Int’l Bus. Machs. Corp.,
`CBM2016-00075, Paper 16 (Dec. 15, 2016) ........................................................68
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ................................................................................................ 2
`
`Merck & Cie v. Gnosis S.p.A.,
`808 F.3d 829 (Fed. Cir. 2015) ........................................................................ 66, 70
`
`Merck & Co. v. Biocraft Labs., Inc.,
`874 F.2d 804 (Fed. Cir. 1989) .................................................................. 33, 41, 59
`
`Merck & Co. v. Teva Pharms. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005) ...................................................................... 69, 70
`
`Microsoft Corp. v. Multi-Tech Sys., Inc.,
`357 F.3d 1340 (Fed. Cir. 2004) .............................................................................12
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`United States Patent No. 9,555,027
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`Microsoft Corp. v. Proxyconn, Inc.,
`789 F.3d 1292 (Fed. Cir. 2015) ...................................................................... 10, 12
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) .............................................................................69
`
`Pfizer v. Apotex,
`480 F.3d 1348 (Fed. Cir. 2007) ..................................................................... passim
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .............................................................................11
`
`Purdue Pharma Prod. L.P. v. Par Pharm., Inc.,
`642 F. Supp. 2d 329 (D. Del. 2009) ......................................................................45
`
`Ricoh Co. v. Quanta Computer Inc.,
`550 F.3d 1325 (Fed. Cir. 2008) .................................................................. 5, 28, 33
`
`SteadyMed Ltd. v. United Therapeutics Corp.,
`IPR2016-00006, Paper 28 (May 12, 2016) ...........................................................68
`
`RULES
`
`37 C.F.R. § 320.22 ...................................................................................................25
`
`37 C.F.R. § 42.100(b) ..............................................................................................10
`
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
`
`EXHIBIT LIST
`
`1001 U.S. Patent No. 9,555,027 (“’027 Patent”)
`1002 Declaration of Professor Graham Buckton (“Buckton Decl.”)
`1003 Curriculum Vitae of Graham Buckton (“Buckton CV”)
`1004 Declaration of Scott Bennett, Ph.D (“Bennett Decl.”)
`1005 Curriculum Vitae of Scott Bennett (“Bennett CV”)
`1006 Declaration of Dr. Adam Kaplin (“Kaplin Decl.”)
`1007 Curriculum Vitae of Adam Ian Kaplin (“Kaplin CV”)
`1008 EP 1 327 440 A1 (“Fujihara”)
`1009 PHARMACEUTICS: THE SCIENCE OF DOSAGE FORM DESIGN (Michael E.
`Aulton ed., 1988) (“Aulton”)
`1010 U.S. Patent No. 4,911,921 (“Denton”)
`1011 K.P.R. Chowdary and N. Rama Rao, Formulation and Evaluation of
`Dispersible Tablets with Pregelatinized Starch, 35 INDIAN DRUGS 368
`(1998) (“Chowdary)
`1012 WO 2004/017973 A1 (“Nakamura”)
`1013 File History for U.S. Patent No. 9,555,027 (“’027 FH”)
`1014 U.S. Patent No. 8,729,085 (“’085 Patent”)
`1015 File History for U.S. Patent No. 8,729,085 (“’085 FH”)
`1016 Morris Bell et al., The Positive and Negative Syndrome Scale and the Brief
`Psychiatric Rating Scale: Reliability, Comparability, and Predictive
`Validity, 180 J. NERVOUS & MENTAL DISEASE 723 (1992) (“Bell”)
`1017 Calculated Fujihara Excipient Ranges
`1018 U.S. Food & Drug Admin., Guidance for Industry: Bioavailability and
`Bioequivalence Studies for Orally Administered Drug Products — General
`Considerations (Mar. 2003) (“2003 FDA Guidance”)
`1019 WO 2004/017973 A1 (Japanese)
`1020 D. Becker et al., Effectiveness of Binders in Wet Granulation: A
`Comparison Using Model Formulations of Different Tabletability, 23 DRUG
`DEVELOPMENT & INDUSTRIAL PHARMACY 791 (1997) (“Becker”)
`1021 HANDBOOK OF PHARMACEUTICAL EXCIPIENTS (Raymond C. Rowe et al.
`eds., 4th ed. 2003) (“Handbook Pharm. Excipients”)
`1022 Rajendra K. Khankari & John Hontz, Chapter 4: Binders and Solvents,
`HANDBOOK OF PHARMACEUTICAL GRANULATION TECH. 59 (Dilip M. Parikh
`ed., 1997) (“Handbook of Pharm. Granulation Tech.”)
`1023 U.S. Patent Application Publication No. US 2004/0186105 (“Allenspach”)
`
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`1024 EP 1 371 646 A1
`1025 Colorcon, Starch 1500: Partially Pregelatinized Maize Starch (1999)
`(“Colorcon Brochure”)
`1026 Martin B. Keller, Improving the Course of Illness and Promoting
`Continuation of Treatment of Bipolar Disorder, 65 J. CLINICAL
`PSYCHIATRY 10 (2004) (“Keller”)
`1027 Mary Kathryn Kottke & Edward M. Rudnic, Chapter 10: Tablet Dosage
`Forms, MODERN PHARMACEUTICS (Gilbert S. Banker & Christopher T.
`Rhodes eds., 4th ed. 2002) (“Modern Pharmaceutics (2002)”)
`1028 Ralph F. Shangraw & Dudley A. Demarest Jr., A Survey of Current
`Industrial Practices in the Formulation and Manufacture of Tablets and
`Capsules, 17 PHARMACEUTICAL TECH. 32 (Jan. 1993) (“Shangraw”)
`1029 Joseph B. Schwartz et al., Intragranular Starch: Comparison of Starch
`USP and Modified Cornstarch, 64 J. PHARMACEUTICAL SCI. 328 (1975)
`(“Schwartz”)
`1030 Charles R. Cunningham & Laura K. Scattergood, Evaluation of a Partially
`Pregelatinized Starch in Comparison with Superdisintegrants in a Direct-
`Compression Hydrochlorothiazide Formulation (Oct. 1999)
`(“Cunningham ”)
`1031 U.S. Patent No. 4,600,579 (“Salpekar”)
`1032 U.S. Patent No. 4,837,031 (“’031 Patent”)
`1033 U.S. Patent No. 6,150,366 (“Arenson”)
`1034 Daniel R. Vanderpoel et al., Adherence to a Fixed-Dose Combination of
`Rosiglitazone Maleate/Metformin Hydrochloride in Subjects with Type 2
`Diabetes Mellitus: A Retrospective Database Analysis, 26 CLINICAL
`THERAPEUTICS 2066 (2004) (“Vanderpoel”)
`1035 U.S. Patent No. 5,605,889 (“Curatolo”)
`1036 EP 1 695 699 A1
`1037 U.S. Patent No. 6,586,617 (“’617 Patent”)
`1038 U.S. Patent No. 7,141,249 (“’249 Patent”)
`1039 U.S. Patent Application Publication No. US 2004/0028741 (“U.S. Pat. App.
`No. 2004/0028741”)
`1040 U.S. Patent No. 8,883,794 (“’794 Patent”)
`1041 File History for U.S. Patent No. 8,883,794 (“’794 FH”)
`1042 Peter Davies, Chapter 11: Oral Solid Dosage Form, PHARMACEUTICAL
`PREFORMULATION AND FORMULATION 379 (Mark Gibson ed., 2001)
`(“Pharmaceutical Preformulation and Formulation”)
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
`
`1043 Vinod P. Shah et al., In Vitro Dissolution Profile Comparison – Statistics
`and Analysis of the Similarity Factor, f2, 15 PHARMACEUTICAL RESEARCH
`889 (1998) (“Shah”)
`1044 Marina Levina & Ali R. Rajabi-Siahboomi, The Influence of Excipients on
`Drug Release from Hydroxypropyl Methylcellulose Matrices, 93 J.
`PHARMACEUTICAL SCI. 2746 (Nov. 2004) (“Levina”)
`1045 Chi-Yuan Wu & Leslie Z. Benet, Predicting Drug Disposition via
`Application of BCS: Transport/Absorption/ Elimination Interplay and
`Development of a Biopharmaceutics Drug Disposition Classification
`System, 22 PHARMACEUTICAL RES. 11 (Jan. 2005) (“Wu”)
`1046 BRITISH PHARMACOPOEIA 2001 (2001)
`1047 21 C.F.R. § 320.22 (April 2005)
`1048 Peter M. Haddad et al., Nonadherence with Antipsychotic Medication in
`Schizophrenia: Challenges and Management Strategy, 5 PATIENT RELATED
`OUTCOME MEASURES 43 (2014)
`1049 U.S. Patent No. 5,047,246 (“’246 Patent”)
`1050 Richard H. Chapman et al., Predictors of Adherence with Antihypertensive
`and Lipid-Lowering Therapy, 165 ARCHIVE INTERNAL MED. 1147 (May
`2005) (“Chapman”)
`1051 DrugBank, Acetaminophen, https://www.drugbank.ca/drugs/DB00316 (last
`visited Apr. 16, 2017)
`1052 William M. Greenberg & Leslie Citrome, Pharmacokinetics and
`Pharmacodynamics of Lurasidone Hydrochloride, a Second-Generation
`Antipsychotic: A Systematic Review of the Published Literature, 56
`CLINICAL PHARMACOKINETICS 493 (2017)
`1053 DrugBank, Valdecoxib, https://www.drugbank.ca/drugs/DB00580 (last
`visited Apr. 14, 2017)
`1054 UNITED STATES PHARMACOPEIA (28th ed. 2005) (“US Pharmacopeia”)
`1055 PubChem, Norfloxacin,
`https://pubchem.ncbi.nlm.nih.gov/compound/norfloxacin#section=Top (last
`visited Apr. 14, 2017)
`1056 U.S. Food & Drug Admin., Orange Book: Approved Drug Products with
`Therapeutic Equivalence Evaluations,
`http://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No
`=003&Appl_No=200603&Appl_type=N (last visited Apr. 13, 2017)
`1057 Barry Blackwell, Treatment Adherence, 129 BRITISH J. PSYCHIATRY 513
`(1976) (“Blackwell”)
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`United States Patent No. 9,555,027
`
`1058 Charles R. Cunningham, Maize Starch and Superdisintegrants in a Direct-
`Compression Formulation, 12 PHARMACEUTICAL MANUFACTURING REVIEW
`23 (Dec. 1999) (“Cunningham II”)
`1059 DrugBank, Piroxicam, https://www.drugbank.ca/drugs/DB00554 (last
`visited Apr. 14, 2017)
`1060 U.S. Patent No. 5,532,372 (“’372 Patent”)
`1061 Product Information – Zeldox (ziprasidone hydrochloride) (Feb. 24, 2016)
`1062 DrugBank, Ibuprofen, https://www.drugbank.ca/drugs/DB01050 (last
`visited Apr. 14, 2017)
`1063 DrugBank, Azithromycin, https://www.drugbank.ca/drugs/ DB00207 (last
`visited Apr. 14, 2017)
`1064 DrugBank, Hydrochlorothiazide, https://www.drugbank.ca/drugs/ DB00999
`(last visited Apr. 14, 2017)
`1065 Center for Drug Evaluation and Research, Application No. 200603,
`Chemistry Reviews – LATUDA (Lurasidone Hydrochloride) Tablets
`1066 U.S. Patent No. 7,727,553 (“’553 Patent”)
`
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`

`Petition for Inter Partes Review
`United States Patent No. 9,555,027
`Petitioner Par Pharmaceutical, Inc. (“Par”) requests inter partes review of
`
`Claims 1-34 of U.S. Patent No. 9,555,027 (“the ’027 Patent,” Ex. 1001), titled
`
`“Pharmaceutical Composition,” which according to USPTO records is assigned to
`
`Sumitomo Dainippon Pharma Co., Ltd. (“Sumitomo”).
`
`I.
`
`
`OVERVIEW
`The Board should grant inter partes review because the ’027 Patent claims
`
`an oral preparation of the drug lurasidone that is obvious in light of what was
`
`known in the pharmaceutical art. The oral preparations claimed in the ’027 Patent
`
`comprise (i) lurasidone; (ii) a water-soluble excipient; (iii) a water-soluble polymer
`
`binder; and (iv) pregelatinized starch. The prior art reference Fujihara teaches oral
`
`preparations comprising (i) lurasidone; (ii) a water-soluble excipient; (iii) a water-
`
`soluble polymer binder, and (iv) disintegrant. The oral preparations claimed in the
`
`’027 Patent are the same as those disclosed in Fujihara, where the disintegrant is
`
`selected to be pregelatinized starch.
`
`This is an obvious choice. Pregelatinized starch was a commonly-used
`
`disintegrant, and was listed in standard pharmaceutical textbooks as one of a small
`
`number of disintegrants that a formulator would use. The purpose of a disintegrant
`
`is to make the tablet disintegrate rapidly, which increases the surface area of tablet
`
`fragments and promotes rapid drug release. Based on Fujihara’s explicit
`
`instructions to incorporate disintegrant in a lurasidone dosage form, one of skill
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`would have thus selected a known disintegrant, and adjusted the amount to obtain
`
`the desired drug release. It was therefore obvious to select pregelatinized starch—
`
`a well-known disintegrant—as the disintegrant in Fujihara’s formulation.
`
`Sumitomo merely used a common disintegrant, in previously-disclosed amounts, to
`
`provide expected results—rapid disintegration and dissolution. KSR Int’l Co. v.
`
`Teleflex Inc., 550 U.S. 398, 417 (2007) (“If a person of ordinary skill can
`
`implement a predictable variation, § 103 likely bars its patentability”).
`
`As this Petition and the accompanying Declarations of Professor Graham
`
`Buckton (Ex. 1002, “Buckton Decl.”) and Dr. Adam Kaplin (Ex. 1006, “Kaplin
`
`Decl.”) set forth, Claims 1-34 (the “Challenged Claims”) of the ’027 Patent are
`
`obvious over Fujihara in view of Aulton (“Ground 1”), and also over Fujihara in
`
`view of Denton and Chowdary (“Ground 2”). Neither Aulton, Denton, nor
`
`Chowdary were before the examiner during prosecution of the ’027 Patent.
`
`Ground 1: Fujihara teaches lurasidone oral preparations comprising
`
`disintegrant. Aulton, a well-known pharmaceutical textbook, teaches a list of 12
`
`common disintegrants including pregelatinized starch. Other references similarly
`
`teach pregelatinized starch as a common disintegrant with beneficial properties,
`
`including rapid dissolution and disintegration in immediate-release formulations of
`
`drugs with similar solubility to lurasidone. One of skill would have selected a
`
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`United States Patent No. 9,555,027
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`common disintegrant such as pregelatinized starch as the disintegrant in Fujihara.
`
`Fujihara also teaches amounts of lurasidone and disintegrant that overlap the
`
`claimed ranges. Fujihara teaches lurasidone content ranging from 0.3%-23.1% by
`
`weight of the total formulation, a first disintegrant from 0.02%-38.1%, and a
`
`second disintegrant from 16.7%-92.3%. These overlap the ranges of lurasidone
`
`(20%-45%) and pregelatinized starch (10%-50%) in the ’027 Patent claims. By
`
`following Fujihara’s teachings and selecting pregelatinized starch as the first or
`
`second disintegrant, or both, one of skill would have arrived at every limitation of
`
`the ’027 Patent claims.
`
`Ground 2: The ’027 Patent claims additionally are obvious over Fujihara in
`
`view of Denton and Chowdary. Fujihara taught lurasidone formulations at dosages
`
`ranging from 5-40 mg. One of skill was motivated to expand this dose range,
`
`because lurasidone was taught to be effective at doses up to 120 mg. As was
`
`common in the field, one of skill was further motivated to make proportionally-
`
`scaled dosages, meaning that different dosage strengths are prepared by using
`
`scaled amounts of a single formulation blend (e.g., a 80 mg dose has double the
`
`amount of every ingredient in a 40 mg dose, which has double the amount in a 20
`
`mg dose). By doing this, one could request that FDA waive the requirement to
`
`separately demonstrate in vivo bioavailability or bioequivalence of every dosage
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`strength, and instead provide an in vivo study for only the highest dose strength
`
`along with much less costly in vitro tests for the lower strengths. To secure this
`
`valuable waiver, one of skill was motivated to formulate dosages of lurasidone
`
`proportionally scaled with respect to all excipients, and having equivalent
`
`dissolution among dosages. One of skill also was motivated to make each scaled
`
`dosage an acceptable size, i.e., to keep smaller doses from being too small to
`
`handle, and to prevent larger doses from being too large to comfortably swallow.
`
`The prior art taught how to accomplish this. Denton taught that ibuprofen,
`
`an active pharmaceutical ingredient (“API” or drug) with similar solubility to
`
`lurasidone, could be formulated into proportionally-scaled formulations across a
`
`wide dosage range with rapid dissolution, equivalent dissolution between dosages,
`
`and reasonable tablet size—by including pregelatinized starch.
`
`
`
`One of skill would have looked to the art to determine the amount of
`
`pregelatinized starch to include in a formulation to obtain rapid dissolution.
`
`Chowdary examined three drugs in formulations with pregelatinized starch ranging
`
`from 5%-50%, and concluded that 10%-20% pregelatinized starch was the
`
`optimum amount for imparting rapid dissolution. Thus, in formulating lurasidone
`
`across the dosage range taught in the art, one of skill would have been motivated
`
`by Denton to select pregelatinized starch (as the disintegrant) in Fujihara’s
`
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`Petition for Inter Partes Review
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`formulations, in an amount between 10%-20% (as Chowdary taught). A skilled
`
`artisan would have had a reasonable expectation of obtaining a formulation
`
`suitable for use across a wide dosage range with rapid dissolution, equivalent
`
`dissolution between dosages, and acceptable tablet size.
`
`Although Fujihara was before the examiner during prosecution, the
`
`examiner allowed Claims 1-34 based on an inaccurate picture of the prior art and
`
`of the known properties of pregelatinized starch.
`
`First, the fact that Fujihara disclosed overlapping ranges of disintegrants and
`
`of lurasidone was not discussed during prosecution. Where a claimed range
`
`overlaps with a range in the prior art, there is a presumption of obviousness. Ricoh
`
`Co. v. Quanta Computer Inc., 550 F.3d 1325, 1331 (Fed. Cir. 2008). And there are
`
`no unexpected results of the claimed ranges to rebut this presumption. As
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`Dr. Buckton explains, one of skill would have understood that a rapidly-dissolving
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`formulation with 20%-45% lurasidone could be achieved by adjusting the amount
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`and type of excipients, including the disintegrant, to obtain the desired dissolution
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`profile. See Buckton Decl. ¶¶ 229-232. The prior art also taught the use of
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`pregelatinized starch within the claimed range to impart rapid dissolution, such that
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`this result was not unexpected.
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`
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`Second, Sumitomo relied on Levina (Ex. 1044) to assert during prosecution
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`that the effect of pregelatinized starch on dissolution is “unpredictable.” This is
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`incorrect. As Dr. Buckton explains, the ’027 Patent claims rapidly-dissolving,
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`immediate-release formulations. But Levina concerns sustained-release
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`formulations of pregelatinized starch included within a sustained-release HPMC
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`gel matrix. Levina teaches that in those particular sustained-release formulations,
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`pregelatinized starch interacts with the sustained-release matrix to form an
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`interlocked gel to slow drug release. This interaction is simply not relevant to the
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`claimed immediate-release formulations, which lack a sustained-release gel matrix.
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`Levina does not teach that pregelatinized starch would retard drug release in
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`immediate-release formulations like those at issue here. Buckton Decl. ¶¶ 124-
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`130.
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`
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`Third, Sumitomo asserted during prosecution that the examiner should
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`disregard highly relevant prior art because the art concerned the use of
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`pregelatinized starch in formulations of drugs other than lurasidone. Again,
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`Sumitomo is wrong. As Dr. Buckton explains, skilled artisans would routinely
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`consider both formulations of lurasidone and formulations of similarly soluble
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`drugs, because solubility was a key parameter when comparing active ingredients.
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`Buckton Decl. ¶¶ 143-145.
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`Fourth, during prosecution Sumitomo asserted that Salpekar (Ex. 1031)
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`taught away from the claimed range (10%-50%) of pregelatinized starch because
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`an example formulation with 18% pregelatinized starch disintegrated slower than
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`two examples with less pregelatinized starch (6.4% and 8.85%). Sumitomo is
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`again incorrect. As Dr. Buckton explains, these examples do not teach away,
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`because there are other differences between these example formulations that
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`contribute to the observed difference in disintegration times. One example
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`contained less lubricant, affecting tablet bonding strength and hardness, and
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`resulting in faster disintegration. Another example contained an additional
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`disintegrant (called a “superdisintegrant” in the reference), leading to enhanced
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`disintegration of that example. It is not possible to attribute, as Sumitomo did,
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`slower disintegration time to the presence of more pregelatinized starch when the
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`other examples also contain less lubricant or include a superdisintegrant. Buckton
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`Decl. ¶¶ 132-139.
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`In light of this new evidence and prior art, the Board should institute review
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`on both distinct proposed grounds and find Claims 1-34 unpatentable.
`
`II.
`
`
`IDENTIFICATION OF CLAIMS BEING CHALLENGED (37 C.F.R.
`§ 42.104(B))
`Ground 1. Claims 1-34 are unpatentable under 35 U.S.C. § 103 as obvious
`
`over Fujihara (Ex. 1008) in view of Aulton (Ex. 1009).
`
`Ground 2. Claims 1-34 are unpatentable under 35 U.S.C. § 103 as obvious
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`over Fujihara (Ex. 1008) in view of Denton (Ex. 1010) and Chowdary (Ex. 1011).
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` OVERVIEW OF THE ’027 PATENT III.
`
`
`Specification
`A.
`The ’027 Patent describes oral preparations of lurasidone containing
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`pregelatinized starch, a water-soluble polymer binder, and a water-soluble
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`excipient. The ’027 Patent also discloses oral preparations that have “equivalent
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`dissolution profile[s] of the active ingredient even though contents of the active
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`ingredient therein are varied,” although only two claims have a dissolution
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`requirement. See ’027 Patent 1:19-23.
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`The ’027 Patent compares the performance of its disclosed oral preparations
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`containing pregelatinized starch with comparative examples lacking pregelatinized
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`starch. E.g., id. 9:40-10:67. It reports that the preparations with pregelatinized
`
`starch had similar dissolution profiles at different strengths, but that a prior-art
`
`formulation without pregelatinized starch had slower dissolution and did not obtain
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`similar dissolution profiles. Id. 10:23-37, Fig. 3. Thus, the ’027 Patent suggests
`
`that including pregelatinized starch can yield higher-dose formulations with rapid
`
`dissolution and equivalent dissolution across dosages.
`
`B.
`
`The ’027 Patent Claims Oral Preparations Comprising 20%-45%
`Lurasidone and 10%-50% Pregelatinized Starch
`
`The ’027 Patent claims are directed to oral preparations of lurasidone,
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`processes by which an oral preparation of lurasidone is prepared, methods for
`
`preparing an oral preparation of lurasidone, and a method of treating schizophrenia
`
`by administering an oral preparation of lurasidone.
`
`Claim 1 recites:
`
`1. An oral preparation, comprising: [lurasidone1], a pregelatinized
`starch; a water-soluble excipient; and a water-soluble polymer binder;
`wherein the content of lurasidone is included in the preparation in an
`amount of from 20 to 45% (wt/wt), and the pregelatinized starch is
`included in the preparation in an amount of from 10 to 50% (wt/wt).
`
`The claims require only the presence of the recited ingredients, and only two
`
`claims further impose a performance requirement. Id. Claims 25, 29. These
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`claims do not require any specific dissolution rate, but only that dissolution rates of
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`different doses are equivalent.
`
` THE PERSON OF ORDINARY SKILL IN THE ART IV.
`
`
`A person of ordinary skill in the art in May 2005 would be a formulator with
`
`
`
`1 “Lurasidone” is N-[ 4-[ 4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-(2R,3R)-2,3-
`
`tetramethylene-butyl]-(1'R,2'S,3'R,4'S)-2,3-bicyclo[2,2,1]heptanedicarboxyimide
`
`hydrochloride. Id. 1:15-18.
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`Petition for Inter Partes Review
`United States Patent No. 9,555,027
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`a Ph.D. in pharmaceutics, or in a drug delivery relevant field of a related discipline
`
`such as physical chemistry, or could have a bachelor’s degree in pharmaceutics, or
`
`in a related field, plus two to five years of relevant experience in developing solid
`
`oral drug formulations. Buckton Decl. ¶ 30. This description is approximate, and
`
`a higher level of education or skill might make up for less experience, and vice
`
`versa. Id. This person may consult with others from an interdisciplinary team,
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`such as a clinician with experience in treating and/or dosing schizophrenic patients.
`
`Id.
`
` CLAIM CONSTRUCTION V.
`
`
`A. Applicable Law
`Because the ’027 Patent has not expired, the Board applies the broadest
`
`reasonable interpretation i