IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`Mylan Laboratories Ltd.
`Petitioner,
`
`v .
`
`Janssen Pharmaceutica NV
`Patent Owner.
`
`U.S. Patent No. 9,439,906 to Vermeulen et al.
`Issue Date: September 13, 2016
`Title: Dosing Regimen Associated with Long
`Acting Injectable Paliperidone Esters
`
`Inter Partes Review No.: IPR2020-00440
`
`Petition for Inter Partes Review of U.S. Patent No. 9,439,906 Under
`35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`I.
`II.
`III.
`
`Page
`INTRODUCTION ........................................................................................... 1
`OVERVIEW .................................................................................................... 1
`STANDING (37 C.F.R. § 42.104(A); PROCEDURAL
`STATEMENTS) .............................................................................................. 4
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ...................................... 4
`A.
`Each Real Party In Interest (37 C.F.R. § 42.8(b)(1)) ............................ 4
`B.
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) .............................. 5
`1.
`Judicial Matters: .......................................................................... 5
`2.
`Administrative Matters: .............................................................. 5
`Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)): ............................................................................................ 5
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(A)) ........................................... 6
`VI. OVERVIEW OF THE ’906 PATENT ............................................................ 6
`A.
`The Claims ............................................................................................ 7
`B.
`The Specification ................................................................................... 8
`VII. CLAIM CONSTRUCTION (37 C.F.R. §§ 42.100(B), 42.104(B)(3)) ........... 8
`VIII. THE CHALLENGED CLAIMS ARE NOT ENTITLED TO CLAIM
`PRIORITY TO DECEMBER 19, 2007 ........................................................... 9
`A.
`The ’918 Provisional Does Not Provide Written Description
`Support For “A First Maintenance Dose” Administered “A
`Month (±7 days) After the Second Loading Dose” ............................10
`
`C.
`
`V.
`
`TABLE OF CONTENTS
`
`i
`
`

`

`IX.
`X.
`XI.
`
`PERSON OF ORDINARY SKILL IN THE ART (“POSA”) .......................13
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)) .................14
`INVALIDITY ANALYSIS ...........................................................................15
`A.
`The Law of Obviousness .....................................................................15
`B.
`The Level of Ordinary Skill in the Pertinent Art ................................16
`C.
`The Scope And Content of the Prior Art .............................................16
`1.
`Depot Antipsychotic Treatments in Schizophrenia ..................16
`2.
`Pharmacokinetics Of Depot Drugs ...........................................18
`a.
`Induction or Loading Dose Regimens ............................18
`b.
`Maintenance Doses .........................................................19
`Paliperidone ..............................................................................20
`3.
`The ’544 Patent .........................................................................21
`4.
`Cleton ........................................................................................22
`5.
`Citrome ......................................................................................24
`6.
`Paliperidone Formulary ............................................................26
`7.
`Ground 1: Claims 1-7, 15 and 17-21 Would Have Been
`Obvious over Citrome, Cleton and the ’544 patent ............................26
`1.
`Claims 1 and 4 ...........................................................................26
`a.
`Preamble: A dosing regimen for administering
`paliperidone palmitate to a psychiatric patient in
`need of treatment for schizophrenia,
`schizoaffective disorder, or schizophreniform
`disorder (claim 1) or psychotic disorder (claim 4)
`comprising ......................................................................26
`Element (1): administering intramuscularly in the
`deltoid of a patient in need of treatment a first
`loading dose of about 150 mg-eq. of paliperidone
`
`D.
`
`b.
`
`ii
`
`

`

`c.
`
`2.
`
`E.
`
`d.
`
`as paliperidone palmitate formulated in a sustained
`release formulation on the first day of treatment ...........29
`Element (2): administering intramuscularly in the
`deltoid muscle of the patient in need of treatment a
`second loading dose of about 100 mg-eq. of
`paliperidone as paliperidone palmitate formulated
`in a sustained release formulation on the 6th to
`about 10th day of treatment ............................................34
`Element (3): administering intramuscularly in the
`deltoid or gluteal muscle of the patient in need of
`treatment a first maintenance dose of about 25 mg-
`eq. to about 150 mg-eq. of paliperidone as
`paliperidone palmitate in a sustained release
`formulation a month (±7 days) after the second
`loading dose ....................................................................37
`Dependent Claims .....................................................................38
`a.
`Claims 2 and 15 ..............................................................38
`b.
`Claims 3 and 5 ................................................................39
`c.
`Claims 6 and 7 ................................................................40
`d.
`Claim 17 ..........................................................................40
`e.
`Claim 18 ..........................................................................42
`f.
`Claims 19-21 ...................................................................42
`Ground 2: Claims 8-14, and 16 Would Have Been Obvious
`Over Citrome, Cleton, the Paliperidone Formulary and the ’544
`patent ...................................................................................................45
`1.
`Claims 8 and 11.........................................................................45
`a.
`Preamble: A dosing regimen for administering
`paliperidone palmitate to a renally impaired
`psychiatric patient in need of treatment for
`schizophrenia, schizoaffective disorder, or
`schizophreniform disorder (claim 8) or psychotic
`disorder (claim 11) comprising.......................................45
`Element (a): administering intramuscularly in the
`deltoid of a renally impaired psychiatric patient in
`need of treatment a first loading dose of from
`about 75 mg-eq. of paliperidone as paliperidone
`
`b.
`
`iii
`
`

`

`c.
`
`d.
`
`palmitate formulated in a sustained release
`formulation on the first day of treatment) ......................45
`Element (b): administering intramuscularly in the
`deltoid muscle of the patient in need of treatment a
`second loading dose of from about 75 mg-eq. of
`paliperidone as paliperidone palmitate formulated
`in a sustained release formulation on the 6th to
`about 10th day of treatment ............................................50
`Element (c): administering intramuscularly in the
`deltoid or gluteal muscle of the patient in need of
`treatment a first maintenance dose of about 25 mg-
`eq. to about 75 mg-eq. (claim 8) or of about 25
`mg-eq. to about 50 mg-eq. (claim 11) of
`paliperidone as paliperidone palmitate in a
`sustained release formulation a month (±7 days)
`after the second loading dose..........................................51
`Dependent Claims .....................................................................52
`a.
`Claims 9 and 16 ..............................................................52
`b.
`Claims 10 and 12 ............................................................53
`c.
`Claims 13 and 14 ............................................................54
`Ground 3: Claims 1-7, 15 and 17-21 Would Have Been
`Obvious over Citrome and the ’544 patent .........................................54
`1.
`Claims 1 and 4 ...........................................................................54
`a.
`Preamble .........................................................................54
`b.
`Element (1) .....................................................................54
`c.
`Element (2) .....................................................................57
`d.
`Element (3) .....................................................................58
`Dependent Claims .....................................................................59
`2.
`Ground 4: Claims 8-14, and 16 Would Have Been Obvious
`Over Citrome, the Paliperidone Formulary and the ’544 patent .........60
`1.
`Claims 8 and 11.........................................................................60
`a.
`Preamble .........................................................................60
`b.
`Element (a) ......................................................................60
`
`2.
`
`F.
`
`G.
`
`iv
`
`

`

`Element (b) .....................................................................61
`c.
`Element (c) ......................................................................62
`d.
`Dependent Claims .....................................................................63
`2.
`No Secondary Considerations of Nonobviousness .............................64
`H.
`XII. THE BOARD SHOULD INSTITUTE TRIAL BASED ON
`MYLAN’S PETITION (35 U.S.C. § 325(D) OR § 314(A)) .........................65
`XIII. CONCLUSION ..............................................................................................67
`
`v
`
`

`

`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Acorda Therapeutics, Inc. v. Roxane Labs., Inc.,
`903 F.3d 1310 (Fed. Cir. 2018) .................................................................... 16, 33
`American Bioscience, Inc. v. Baker Norton Pharm., Inc.,
`2002 WL 54627 (C.D. Cal. 2002) ...................................................................... 47
`Amgen Inc. v. Alexion Pharmaceuticals Inc.,
`IPR2019-00740, Paper 15 (P.T.A.B. Aug. 20, 2019) ......................................... 66
`Amgen Inc. v. F. Hoffman-La Roche, Ltd.,
`580 F.3d 1340 (Fed. Cir. 2009) .................................................................... 32, 57
`Amneal Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc.,
`IPR2013-00368, Paper 8 (P.T.A.B. Dec. 2013) ................................................. 65
`Apotex Inc. v. UCB Biopharma SPRL,
`IPR2019-00400, Paper 17 (P.T.A.B. July 15, 2019) .......................................... 68
`Ariad Pharm., Inc. v. Eli Lilly and Co.,
`598 F.3d 1336 (Fed. Cir. 2010) (en banc) .......................................................... 10
`Arkema Inc. v. Honeywell Int’l, Inc.,
`PGR2016-00011, Paper No. 13 (P.T.A.B. Sept. 2, 2016) .................................. 10
`Becton, Dickinson and Company v. B. Braun Melsungen AG,
`IPR2017-01586, slip op. (P.T.A.B. Dec. 15, 2017) ........................................... 66
`Celltrion, Inc. v. Biogen, Inc.,
`IPR2017-01095, Paper No. 60 (P.T.A.B. Oct. 4, 2018) ..................................... 10
`Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc.,
`807 F.2d 955 (Fed. Cir. 1986) ............................................................................ 13
`Dr. Reddy’s Labs. S.A. v. Indivior UK Ltd.,
`IPR2019-00329, Paper 21 (P.T.A.B. June 3, 2019) ..................................... 10, 11
`DuPont de Nemours & Co. v. Synvina C.V.,
`904 F.3d 996 (Fed. Cir. 2018) .....................................................................passim
`
`vi
`
`

`

`Duramed Pharm., Inc. v. Watson Labs., Inc.,
`413 F. App’x 289 (Fed. Cir. 2011) ..................................................................... 15
`Dystar Textilfarben GmbH v. C.H. Patrick Co.,
`464 F.3d 1356 (Fed. Cir. 2006) .......................................................................... 28
`Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd.,
`533 F.3d 1353 (Fed. Cir. 2008) .......................................................................... 28
`Eiselstein v. Frank,
`52 F.3d 1035 (Fed. Cir. 1995) ...................................................................... 11, 12
`Graham v. John Deere Co. of Kansas City,
`383 U.S. 1 (1966) ................................................................................................ 15
`Grünethal GmbH v. Antecip Bioventures II LLC,
`PGR2017-00008, Paper No. 43 (P.T.A.B. June 22, 2018) ................................. 11
`Hulu, LLC v. Sound View Innovations, LLC,
`IPR2018-01039 (P.T.A.B. Dec. 20, 2019) ................................................... 22, 23
`HyperBranch Medical Technology, Inc. v. Confluent Surgical, Inc.,
`IPR2018-01099, Paper 14 (P.T.A.B. Nov. 27, 2018) ......................................... 66
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) ...................................................................passim
`In re Cyclobenzaprine Hydrochloride,
`676 F.3d 1063 (Fed. Cir. 2012) ........................................................ 36, 57, 58, 59
`In re Lukach,
`442 F.2d 967 (C.C.P.A. 1971) .............................................................................. 9
`In re Montgomery,
`677 F.3d 1375 (Fed. Cir. 2012) .................................................................... 26, 27
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) ...................................................................passim
`In re Wertheim,
`541 F.2d 257 (C.C.P.A. 1976) ............................................................................ 11
`
`vii
`
`

`

`In re Wesslau,
`353 F.2d 238 (C.C.P.A. 1965) ............................................................................ 15
`Janssen Pharmaceuticals, Inc. et al. v. Mylan Laboratories Ltd.,
`1-19-cv-00153 (N.D. W. Va.) ............................................................................... 5
`Janssen Pharmaceuticals, Inc. et al. v. Mylan Laboratories Ltd.,
`1-19-cv-01488 (D. Del.) ....................................................................................... 5
`Janssen Pharmaceuticals, Inc. et al. v. Mylan Laboratories Ltd.,
`2-19-cv-16484 (D.N.J.) ......................................................................................... 5
`Janssen Pharmaceuticals, Inc. et al. v. Pharmascience Inc. et al.,
`1-19-cv-02313 (D. Del.) ....................................................................................... 5
`Janssen Pharmaceuticals, Inc. et al. v. Pharmascience Inc. et al.,
`Case No. 2-19-cv-21590 (D.N.J.) ......................................................................... 5
`
`Janssen Pharmaceuticals, Inc. et al v. Teva Pharmaceuticals USA,
`Inc. et al.,
`2-18-cv-00734 (D.N.J.) ..................................................................................... 5, 8
`Kashiv Biosciences, LLC v. Amgen Inc.,
`IPR2019-00791, Paper 15 (P.T.A.B. Sept. 11, 2019)................................... 67, 68
`
`Koios Pharms. LLC v. medac Gesellschaft für klinische
`Spezialpräparate mbH,
`IPR2016-01370, Paper 13 at 35 (P.T.A.B. Feb. 8, 2017) ................................... 65
`KSR Int’l Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007) .....................................................................................passim
`Medichem, S.A. v. Rolabo, S.L.,
`437 F.3d 1157 (Fed. Cir. 2006) .......................................................................... 15
`Mylan Pharmaceuticals Inc. v. Sanofi-Aventis Deutschland GMBH,
`IPR2018-01680, Paper 22 (P.T.A.B. Apr. 3, 2019) ........................................... 67
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) ............................................................................ 65
`NHK Spring Co., Ltd. v. Intri-Plex Techs., Inc.,
`Case IPR2018-00752, Paper 8 (P.T.A.B. Sept. 12, 2018) .................................. 67
`
`viii
`
`

`

`One World Technologies Inc. v. The Chamberlain Group Inc.,
`IPR2017-00126, Paper 67 (P.T.A.B. April 4, 2019) ............................ 2, 8, 38, 40
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ...................................................................... 4, 65
`Pharmacosmos A/S v. Luitpold Pharms., Inc.,
`IPR2015-01490, Paper 54 (P.T.A.B. Jan. 4, 2017) ................................ 29, 30, 54
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc) ............................................................ 8
`PowerOasis, Inc. v. T-Mobile USA, Inc.,
`522 F.3d 1299 (Fed. Cir. 2008) .......................................................................... 10
`Quanergy Systems, Inc. v. Velodyne Lidar, Inc.,
`IPR2018-00256, Paper 14 (P.T.A.B. May 25, 2018) ......................................... 65
`Soft Gel Technologies, Inc. v. Jarrow Formulas, Inc.,
`864 F.3d 1334 (Fed. Cir. 2017) .......................................................................... 33
`Valve Corp. v. Elec. Scripting Prods., Inc.,
`IPR2019-00062, -00063, -00084, Paper 11 (P.T.A.B. Apr. 2, 2019) ................. 67
`Vas-Cath Inc. v. Mahurkar,
`935 F.2d 1555 (Fed. Cir. 1991) .......................................................................... 10
`Warner Chilcott Co., LLC v. Teva Pharmaceuticals USA, Inc.,
`642 F. App’x 996 (Fed. Cir. 2016) ......................................................... 31, 56, 57
`Watson Labs., Inc. v. United Therapeutics Corp.,
`IPR2017-01621, Paper 33 (P.T.A.B. Mar. 26, 2018) ................................... 23, 24
`Statutes
`35 U.S.C. § 100 et. seq. ............................................................................................ 14
`35 U.S.C. § 102(a) ................................................................................................... 22
`35 U.S.C. § 102(b) ................................................................................. 21, 24, 25, 26
`35 U.S.C. § 103 .................................................................................................... 3, 36
`35 U.S.C. § 112 .......................................................................................................... 9
`
`ix
`
`

`

`Regulations
`37 C.F.R. § 42.6(d) .................................................................................................. 14
`37 C.F.R. § 42.10(b) .................................................................................................. 4
`37 C.F.R. § 42.63(e) ................................................................................................... 4
`37 C.F.R. § 42.100(b) ............................................................................................ 8, 9
`37 C.F.R. § 42.106(a) ................................................................................................. 4
`Other Authorities
`MPEP 2163.05(III) ................................................................................................... 11
`
`x
`
`

`

`Petitioner’s Exhibit List
`
`Exhibit #
`
`Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`1006
`
`1007
`
`1008
`1009
`
`1010
`
`1011
`
`1012
`
`U.S. Patent No. 9,439,906 (“the ’906 patent”)
`
`Declaration of Mansoor M. Amiji, Ph.D., R.Ph.
`
`Abstracts of the Annual Meeting of the American Society for
`Clinical Pharmacology and Therapeutics, 83 Supp. 1 Clin.
`Pharmacol. & Therapeutics S31, PI-74 and PI-75 (Mar. 2008)
`(“Cleton”)
`
`L. Citrome, Paliperidone: quo vadis?, Int. J. Clin. Pract. 61(1):653-
`662 (Apr. 2007) (“Citrome”)
`U.S. Patent No. 6,555,544 (“the ’544 patent”)
`Formulary Drug Reviews – Paliperidone, Hospital pharmacy
`42(7):637-647 July 2007 (“Paliperidone Formulary”)
`N. Washington, C. Washington, C. Wilson. Physiological
`Pharmaceutics: Barriers to Drug Absorption. (2001), pages 26-29
`(“Physiological Pharmaceutics”)
`U.S. Patent No. 6,495,534 (“the ’534 patent”)
`J.M. Kane, et al. Guidelines for depot antipsychotic treatment in
`schizophrenia. B. Eur. Neuropharmacol. 8(1):55-65 (1995)
`(“Kane”)
`N. Marder, et al. Pharmacokinetics of long-acting injectable
`neuroleptic drugs: clinical implications. Psychopharmacology.
`98:433-439 (1989) (“Marder”)
`
`M.E. Aulton. Pharmaceutics: The Science of Dosage Form Design
`(2002), Chapter 19 (“Aulton”)
`
`Comparison of the ’276 and the ’918 provisional application
`specifications (“Specification Comparison”)
`
`vi
`
`

`

`Exhibit #
`
`Description
`
`1013
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`1024
`
`1025
`1026
`1027
`
`U.S. Patent No. 5,254,556 (“the ’556 patent”)
`
` U.S. Patent No. 7,449,184 (“the ’184 patent”)
`
`R. Urso, P. Blardi, G. Giorgi. A short introduction to
`pharmacokinetics, Rev. Med. Pharmacol. Sci. 6: 33-44 (2002)
`(“Urso”)
`U.S. Provisional Application No. 61/014,918 (“the ’918
`provisional”)
`U.S. Provisional Application No. 61/120,276 (“the ’276
`provisional”)
`Excerpt of ’906 Patent Prosecution History (“6-12-2016
`Amendment and Response”)
`
`’906 Patent Prosecution History
`
`L. Ereshefsky, et al., Future of Depot Neuroleptic Therapy:
`Pharmacokinetic and Pharmacodynamic Approaches. J. Clin.
`Psychiatry, 45(5):50-59 (1984) (“Ereshefsky”)
`Goodman & Gilman’s, The Pharmacological Basis of Therapeutics
`(2001), Chapter 1 (“Goodman & Gilman”)
`D. Waller & A. Renwick, Principles of Medical Pharmacology
`(1994) (“Principles of Medical Pharmacology”)
`U.S. Patent No. 6,818,633 (“the ’633 patent”)
`
`Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery
`Systems 8th ed. (2005) (“Added Substances”)
`Orange Book Entry for Invega Sustenna®
`
`Excerpt of ’906 Patent Prosecution History (“11-11-2015 IDS”)
`
`Curriculum Vitae of Dr. Mansoor Amiji
`
`vii
`
`

`

`Exhibit #
`
`Description
`
`1028
`
`1029
`
`1030
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`Janssen Pharmaceuticals, Inc. et al v. Teva Pharmaceuticals USA,
`Inc. et al., 2-18-cv-00734 (D.N.J.) (“Joint Claim Construction”)
`Janssen Pharmaceuticals, Inc. et al v. Teva Pharmaceuticals USA,
`Inc. et al., 2-18-cv-00734 (D.N.J.) (“Claim Construction
`Agreement”)
`INVEGA SUSTENNA® Label (“INVEGA LABEL”)
`
`ClinicalTrials.gov, A Safety and Tolerability Study of Paliperidone
`Palmitate Injected in the Shoulder or the Buttock Muscle in
`Patients With Schizophrenia (July 2006),
`https://clinicaltrials.gov/ct2/history/NCT00119756?V_10=View#St
`udyPageTop (“NCT00119756”)
`ClinicalTrials.gov, A Study to Evaluate the Effectiveness and
`Safety of 3 Doses of Paliperidone Palmitate in Treating Subjects
`With Schizophrenia (October 2006),
`https://clinicaltrials.gov/ct2/history/NCT00210548?V_11=View#St
`udyPageTop (“NCT00210548”)
`
`ClinicalTrials.gov, Safety and Efficacy of an Anti-Psychotic
`Versus Placebo in Subjects With Schizophrenia (November 2005),
`https://clinicaltrials.gov/ct2/history/NCT00101634?V_4=View#Stu
`dyPageTop (“NCT00101634”)
`
`ClinicalTrials.gov, A Study to Compare the Effectiveness and
`Safety of Flexibly Varied Doses of Paliperidone Palmitate and
`Risperidone in Treating Patients With Schizophrenia (July 2006),
`https://clinicaltrials.gov/ct2/history/NCT00210717?V_10=View#St
`udyPageTop (“NCT00210717”)
`
`ClinicalTrials.gov, Intramuscular Injections of Paliperidone
`Palmitate in the Arm or Buttock of Subjects With Schizophrenia
`(June 2005),
`https://clinicaltrials.gov/ct2/history/NCT00073320?V_1=View#Stu
`dyPageTop (“NCT00073320”)
`
`viii
`
`

`

`Exhibit #
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`Description
`
`ClinicalTrials.gov, Evaluate the Efficacy in the Prevention of
`Recurrence of the Symptoms of Schizophrenia (April 2006),
`https://clinicaltrials.gov/ct2/history/NCT00111189?V_3=View#Stu
`dyPageTop (“NCT00111189”)
`Guarino, Richard A. “Clinical research protocols.” New Drug
`Approval Process. CRC Press, 2004, pages 257-61
`Bishara, Delia, and David Taylor. “Upcoming agents for the
`treatment of schizophrenia.” Drugs 68.16 (2008): 2269-2292
`Kramer, M., et al. “322–Efficacy/tolerability of paliperidone
`palmitate: 9-week, placebo-controlled study in schizophrenia
`patients.” Schizophrenia Research 98 (2008): 165-166
`
`’906 Patent Specification as Filed
`
`Kramer M, Litman R, Lane R, et al. “908. Efficacy and tolerability
`of two fixed dosages of paliperidone palmitate in the treatment of
`schizophrenia: results of a 9-week placebo-controlled trial.” Biol
`Psychiatry 2008;63:1S-319S
`
`Declaration of Laboratory Research Analyst Alys Tryon
`
`Nankivell, Brian J. Creatinine clearance and the assessment of
`renal function. Australian Prescriber, 2001
`
`Perry, Paul J., ed. Psychotropic drug handbook. Lippincott Williams
`& Wilkins, 2007, pages 74-77
`
`Traynor, Jamie, et al. How to measure renal function in clinical
`practice. Bmj 333.7571 (2006): 733-737
`Janicak, Philip G., and Elizabeth A. Winans. Paliperidone ER: a
`review of the clinical trial data. Neuropsychiatric disease and
`treatment 3.6 (2007):869
`
`ix
`
`

`

`Exhibit #
`
`Description
`
`1047
`
`Physicians’ Desk Reference (2002), HALDOL® Decanoate
`
`x
`
`

`

`I.
`
`INTRODUCTION
`Mylan Laboratories Ltd. (“Petitioner”) petitions for Inter Partes Review,
`
`seeking cancellation of Claims 1-21 (“challenged claims”) of U.S. Patent No.
`
`9,439,906 (“the ’906 patent”) (EX1001), assigned to Janssen Pharmaceutica NV
`
`(“Patent Owner”).
`
`II. OVERVIEW
`The challenged claims of the ’906 patent are nothing more than the results of
`
`routine optimization of dosing amounts of paliperidone palmitate reported in the
`
`prior art. For example, Figure 2 of the ’906 patent (which falls within the scope of
`
`the challenged claims) states that the injectable dosing regimen of paliperidone
`
`palmitate is administered on days 1, 8, 36 and 64. The prior art repeatedly teaches
`
`this identical dosing schedule for paliperidone palmitate. EX1002 ¶¶70-75;
`
`EX1004, Table 1; EX1003, PI-75.
`
`Citrome discloses that in Phase III study, intramuscular depot injections of
`
`50, 100 or 150 mg-eq. paliperidone as paliperidone palmitate were administered on
`
`days 1, 8, 36 and 64 of therapy. EX1002 ¶¶70-75; EX1004, Table 1; see also
`
`EX1038, 2286 (discussing “significant improvement” with 50 or 100 mg eq. on
`
`Days 1, 8 and 36). Citrome also discloses that in another Phase III study, a range
`
`of 25-100 mg-eq. was administered every four weeks (over a 52-week period).
`
`EX1002 ¶¶70-75; EX1004, Table 1. In another Phase III study, doses of 25, 50,
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`1
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`100, or 150 mg-eq. were administered. EX1004, Table 1. Additionally, Cleton
`
`discloses that a dose of “25-150 mg-eq.” was well-tolerated and resulted in low
`
`treatment-emergent adverse events. EX1002 ¶¶66-69; EX1003, PI-74. Thus, the
`
`combined teachings of the clinical trials in Citrome and Cleton recurrently teach
`
`that a range of 25-150 mg-eq. paliperidone as paliperidone palmitate is safe and
`
`effective to administer to humans. This dosing range overlaps with the ranges
`
`recited in the challenged claims. DuPont de Nemours & Co. v. Synvina C.V., 904
`
`F.3d 996, 1006 (Fed. Cir. 2018) (“[A] prima facie case of obviousness typically
`
`exists when the ranges of a claimed composition overlap the ranges disclosed in
`
`the prior art.”).
`
`In view of the dosages and the dosing schedule disclosed in the prior art,
`
`arriving at the claimed invention would have been nothing more than routine
`
`experimentation for a person of ordinary skill in the art (“POSA”). In re Peterson,
`
`315 F.3d 1325, 1330 (Fed. Cir. 2003) (explaining that the normal desire of artisans
`
`to improve upon what is already generally known provides the motivation to
`
`determine optimum amounts). Indeed, this would not have been a challenge for
`
`the POSA—the ’906 patent freely admits this: “[t]hose of skill in the treatment of
`
`diseases could easily determine the effective amount of paliperidone to administer
`
`for the treatment of the diseases listed above.” EX1001, 14:13-15; EX1002 ¶97;
`
`One World Technologies Inc. v. The Chamberlain Group Inc., IPR2017-00126,
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`2
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`

`

`Paper 67 at 14-16 (P.T.A.B. April 4, 2019) (“admissions in a patent may be
`
`considered prior art for any purpose, including as evidence of obviousness under
`
`35 U.S.C. §103”).
`
`As for determining the dosage on each day, the POSA would have been
`
`guided by well-known principles involving injectable depot formulations. EX1002
`
`¶¶44-50. The initial objective is to administer depots so that the requisite blood
`
`level of the medication is reached quickly. EX1002 ¶47; EX1004, 660. This is
`
`done by front-loading the dosing with higher amounts of the depot drug known as
`
`the “loading dose”. EX1002 ¶47; EX1011, 284-85. The “loading dose” can be
`
`given in one or more doses. EX1002 ¶48; EX1021, 27; EX1046, 882 (stating that
`
`“[t]he first two paliperidone palmitate injections will be administered as a loading
`
`dose within 7 days of initiation”); EX1044, 76 (haloperidol decanoate may be split
`
`into two loading doses administered 3 to 7 days apart); EX1047, 5 (same).
`
`Once the initial requisite blood levels of the medication are reached through
`
`the loading dose, the objective becomes to “obtain a sufficiently constant delivery
`
`of the drug from the depot, so that the serum level is kept as constant as possible
`
`between injections.” EX1002 ¶49; EX1009, 61; EX1011, 284-85. This is done by
`
`providing smaller “maintenance doses” at regular intervals. EX1002 ¶49; EX1011,
`
`285. By administering maintenance doses following the initial dose, therapeutic
`
`steady-state plasma concentrations are achieved more rapidly than if simply giving
`
`3
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`doses of equal size and at identical dosage time intervals. EX1002 ¶49; EX1011,
`
`285. Where the general conditions of a claim are disclosed in the prior art, it is not
`
`inventive to discover the optimum or workable ranges of a result-effective variable
`
`through routine experimentation. In re Applied Materials, Inc., 692 F.3d 1289,
`
`1295 (Fed. Cir. 2012); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368 (Fed. Cir.
`
`2007) (“[D]iscovery of an optimum value of a variable in a known process is
`
`usually obvious.”).
`
`III.
`
`STANDING (37 C.F.R. § 42.104(A); PROCEDURAL STATEMENTS)
`Petitioner certifies that (1) the ’906 patent is available for IPR; and
`
`(2) Petitioner is not barred or estopped from requesting IPR of any claim of the
`
`’906 patent on the grounds identified herein. This Petition is filed in accordance
`
`with 37 C.F.R. § 42.106(a). Concurrently filed herewith are a Power of Attorney
`
`and an Exhibit List pursuant to § 42.10(b) and § 42.63(e), respectively. The
`
`required fee is paid through, and the Office is authorized to charge any fee
`
`deficiencies and credit overpayments to, Deposit Acct. No. DA501290 (Customer
`
`ID No. 27160).
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`A.
`Each Real Party In Interest (37 C.F.R. § 42.8(b)(1))
`The real parties in interest for this petition are Mylan Laboratories Ltd.,
`
`Mylan Institutional LLC, Mylan Pharmaceuticals Inc., Mylan Inc., and Mylan N.V.
`
`4
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`

`

`B.
`
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2))
`1.
`Judicial Matters:
`Petitioner is aware of the following district court actions involving the ’906
`
`patent: Janssen Pharmaceuticals, Inc. et al v. Teva Pharmaceuticals USA, Inc. et
`
`al., 2-18-cv-00734 (D.N.J.); Janssen Pharmaceuticals, Inc. et al. v. Mylan
`
`Laboratories Ltd., 2-19-cv-16484 (D.N.J.); Janssen Pharmaceuticals, Inc. et al. v.
`
`Mylan Laboratories Ltd., 1-19-cv-00153 (N.D. W. Va.); Janssen Pharmaceuticals,
`
`Inc. et al. v. Mylan Laboratories Ltd., 1-19-cv-01488 (D. Del.); Janssen
`
`Pharmaceuticals, Inc. et al. v. Pharmascience Inc. et al., Case No. 2-19-cv-21590
`
`(D.N.J.); Janssen Pharmaceuticals, Inc. et al. v. Pharmascience Inc. et al., 1-19-
`
`cv-02313 (D. Del.).
`
`Administrative Matters:
`2.
`The Public Patent Application Information Retrieval (PAIR) website
`
`indicates that there are no related United States patents or pending applications.
`
`C.
`
`Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)):
`Lead Counsel
`Jitendra Malik, Ph.D.
`Reg. No. 55,823
`Katten Muchin Rosenman LLP
`550 S. Tryon Street, Suite 2900
`Charlotte, NC 28202-4213
`jitty.malik@katten.com
`
`Back-Up Counsel
`Guylaine Haché, Ph.D.
`Reg. No. 76,083
`Jillian Schurr (pro hac vice to be filed)
`Katten Muchin Rosenman LLP
`525 W. Monroe Street
`Chicago, IL 60661-3693
`guylaine.hache@katten.com
`jillian.schurr@katten.com
`
`5
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`

`

`Alissa M. Pacchioli
`Reg. No. 74,252
`Katten Muchin Rosenman LLP
`550 S. Tryon Street, Suite 2900
`Charlotte, NC 28202-4213
`alissa.pacchioli@katten.com
`
`Lance Soderstrom
`Reg. No. 65,405
`Katten Muchin Rosenman LLP
`575 Madison Avenue
`New York, NY 10022-2585
`lance.soderstrom@katten.com
`
`Petitioner consents to email service as indicated above.