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
`
`Declaration of Mansoor M. Amiji, Ph.D., R.Ph.
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Mylan v. Janssen (IPR2020-00440) Ex. 1002 p. 001
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`

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`Declaration of Dr. Mansoor M. Amiji
`
`Table of Contents
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`INTRODUCTION ...................................................................................... 1
`
`MY EXPERIENCE AND QUALIFICATIONS ......................................... 2
`
`LIST OF MATERIALS CONSIDERED .................................................... 9
`
`LEGAL STANDARD ...............................................................................14
`
`A. Obviousness ..............................................................................................14
`
`PERSON OF ORDINARY SKILL IN THE ART (“POSA”) ....................18
`
`BACKGROUND OF RELEVANT TECHNICAL CONCEPTS ...............20
`
`A. Pharmacokinetics and Drug Metabolism ...................................................20
`
`B. Depot Formulations and Related Pharmacokinetics and Drug
`Metabolism Concepts ................................................................................23
`
`C. Paliperidone and Its Use for Treatment of Patients with Schizophrenia .....26
`
`THE ’906 PATENT ...................................................................................27
`
`CLAIM CONSTRUCTION .......................................................................38
`
`OBVIOUSNESS .......................................................................................39
`
`A. Ground 1: Claims 1-7, 15 and 17-21 Would Have Been Obvious over
`Citrome, Cleton, and the ’544 Patent .........................................................40
`
`1. The Scope and Content of the Prior Art .................................................40
`
`a) The ’544 Patent (EX1005) ..................................................................40
`
`b) Cleton (EX1003) ................................................................................41
`
`c) Citrome (EX1004) ..............................................................................43
`
`2. The Differences Between the Claims and Prior Art ...............................46
`
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`Declaration of Dr. Mansoor M. Amiji
`
`a) Claims 1 and 4 ....................................................................................46
`
`b) Claims 2 and 15 ..................................................................................58
`
`c) Claims 3 and 5 ....................................................................................62
`
`d) Claims 6 and 7 ....................................................................................62
`
`e) Claim 17 .............................................................................................63
`
`f) Claim 18 .............................................................................................66
`
`g) Claims 19-21 ......................................................................................67
`
`B. Ground 2: Claims 8-14 and 16 Would Have Been Obvious Over Citrome,
`Cleton, the Paliperidone Formulary and the ’544 Patent ............................71
`
`1. The Scope and Content of the Prior Art .................................................71
`
`a) The ’544 Patent ..................................................................................71
`
`b) Cleton (EX1003) ................................................................................71
`
`c) Citrome (EX1004) ..............................................................................71
`
`d) Paliperidone Formulary (EX1006) ......................................................71
`
`2. The Differences Between the Claims and Prior Art ...............................72
`
`a) Claims 8 and 11 ..................................................................................72
`
`b) Claims 9 and 16 ..................................................................................81
`
`c) Claims 10 and 12 ................................................................................83
`
`d) Claims 13 and 14 ................................................................................83
`
`C. Ground 3: Claims 1-7, 15 and 17-21 Would Have Been Obvious over
`Citrome and the ’544 Patent ......................................................................84
`
`1. The Scope and Content of the Prior Art .................................................84
`
`a) The ’544 Patent (EX1005) ..................................................................84
`
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`Declaration of Dr. Mansoor M. Amiji
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`b) Citrome (EX1004) ..............................................................................84
`
`2. The Differences Between the Claims and Prior Art ...............................84
`
`a) Claims 1 and 4 ....................................................................................84
`
`b) Dependent Claims ..............................................................................90
`
`D. Ground 4: Claims 8-14 and 16 Would Have Been Obvious Over Citrome,
`the Paliperidone Formulary and the ’544 Patent ........................................91
`
`3. The Scope and Content of the Prior Art .................................................91
`
`a) The ’544 Patent (EX1005) ..................................................................91
`
`b) Citrome (EX1004) ..............................................................................92
`
`c) Paliperidone Formulary (EX1006) ......................................................92
`
`4. The Differences Between the Claims and Prior Art ...............................92
`
`a) Claims 8 and 11 ..................................................................................92
`
`b) Dependent Claims ..............................................................................98
`
`10.
`
`SECONDARY CONSIDERATIONS ........................................................98
`
`iii
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`I, Mansoor M. Amiji, Ph.D., R.Ph. do hereby declare and state as follows:
`
`1.
`
`I have been asked to provide testimony as to what one of ordinary skill
`
`in the art would have understood with respect to the patent at issue and various prior
`
`art discussed herein. I provide this testimony below:
`
`1.
`
`INTRODUCTION
`
`2.
`
`I am over the age of eighteen (18) and otherwise competent to make
`
`this declaration.
`
`3.
`
`I have been retained as an expert witness on behalf of Petitioner Mylan
`
`Laboratories Ltd. for the above captioned inter partes review (“IPR”). I am being
`
`compensated for my time in connection with this IPR at my standard consulting rate,
`
`which is $750.00 per hour. My compensation is in no way dependent on the outcome
`
`of this IPR.
`
`4.
`
`I understand that the petition for IPR involves U.S. Patent No.
`
`9,439,906 (“the ’906 patent”) (EX1001).
`
`5.
`
`The ’906 patent names An Vermeulen and Alfons Wouters as the
`
`purported inventors.
`
`1
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`Declaration of Dr. Mansoor M. Amiji
`
`6.
`
`For the purposes of this declaration, I have been told to assume the
`
`relevant priority date of the ’906 patent is December 5, 20081—the filing date of
`
`U.S. Provisional Application No. 61/120,276. I further understand that the ’906
`
`patent is assigned to Janssen Pharmaceutica NV (“Janssen,” “Patentee,” or “Patent
`
`Owner”).
`
`7.
`
`As explained below, it is my opinion that Claims 1-21 of the ’906 patent
`
`would have been obvious to the skilled artisan as of the time of the priority date of
`
`the ’906 patent. Therefore, these claims are invalid.
`
`2. MY EXPERIENCE AND QUALIFICATIONS
`
`8.
`
`I am an expert in the field of pharmaceutical sciences and
`
`pharmacokinetics. Specifically, I specialize in drug formulation development and
`
`targeted delivery of therapeutics, and I have been an expert in this field since prior
`
`to 2008. I have relied upon my training, knowledge, and experience in the relevant
`
`art to form my opinions.
`
`1 I have not been asked to analyze whether this is indeed the correct priority
`
`date but rather assume that it is for the purposes of my declaration. However, should
`
`this become an issue during the proceeding, I may be called upon to offer my
`
`opinion.
`
`2
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`Declaration of Dr. Mansoor M. Amiji
`
`9.
`
`In 1988, I graduated with honors from Northwestern University and
`
`received a Bachelor of Science degree in Pharmacy and became a Registered
`
`Pharmacist in Massachusetts. In 1992, I received a Ph.D. in Pharmaceutical
`
`Science/Pharmaceutics from the School of Pharmacy and Pharmaceutical Sciences
`
`at Purdue University, under the supervision of Professor Kinam Park. My
`
`dissertation focused on biomaterials and water-soluble polymers. During my
`
`graduate studies at Purdue University, I took several pharmaceutics courses and had
`
`hands-on training in pharmaceutical formulations.
`
`10.
`
`I am currently a University Distinguished Professor and Professor of
`
`Pharmaceutical Sciences in the School of Pharmacy, Bouve College of Health
`
`Sciences at Northeastern University in Boston, Massachusetts. I am also jointly
`
`appointed as a Professor of Chemical Engineering in the College of Engineering at
`
`Northeastern University. I am also currently an Affiliate Faculty Member in the
`
`Department of Biomedical Engineering at Northeastern University. I have taught
`
`and carried out research in pharmaceutical sciences at Northeastern University since
`
`1993, and from 2010 to 2016, I served as the Chairman of the Department of
`
`Pharmaceutical Sciences. In 2000, I was a Visiting Research Scholar in the
`
`Department of Chemical Engineering at the Massachusetts Institute of Technology
`
`(MIT) in Cambridge, Massachusetts, in the laboratory of Professor Robert Langer.
`
`3
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`Declaration of Dr. Mansoor M. Amiji
`
`11. As a tenured faculty member at Northeastern University, I have over 27
`
`years of experience in teaching drug formulations to both graduate and
`
`undergraduate students. In theory and laboratory courses that I have taught and
`
`continue to teach, I extensively cover the manufacturing and composition of
`
`pharmaceutical formulations, delivery systems and pharmacokinetics. I also serve as
`
`a consultant to several pharmaceutical, biotechnology, and medical device
`
`companies regarding product development and drug delivery.
`
`12. Over the course of my career I have published extensively and am
`
`ranked as a Thompson-Reuters Highly Cited (top 1%) author in Pharmacology and
`
`Toxicology. I have coauthored over 60 book chapters and more than 350 peer
`
`reviewed scientific articles. I am also an inventor on several issued United States
`
`patents. The topics of these materials including the design and development of
`
`pharmaceutical dosage forms, pharmacokinetics, drug metabolism, dose delivery
`
`and controlled research systems and the use/formulation of related excipients and
`
`methods. I have been involved in and consulted on multiple projects over the years
`
`both in industry and academia about the aforementioned topics. To that end, I have
`
`taught courses in pharmaceutics; drug design, evaluation, and development; dosage
`
`forms; and pharmacokinetics.
`
`13.
`
`I have served as a grant reviewer for the National Institutes of Health,
`
`the Department of Defense, the United States Department of Agriculture, and the
`
`4
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`Declaration of Dr. Mansoor M. Amiji
`
`American Chemical Society. I am a member of several professional and industrial
`
`societies, including the American Association of Pharmaceutical Sciences (AAPS)
`
`and the Controlled Release Society (CRS), and have participated as a reviewer for
`
`more than 50 scientific journals. I have also received a number of professional
`
`awards and honors, including the Nano Science and Technology Institute (NSTI)
`
`Fellowship Award for Outstanding Contributions towards the Advancement in
`
`Nanotechnology, Microtechnology, and Biotechnology in 2006; a Fellowship and
`
`Meritorious Manuscript Award from the AAPS in 2007; the Tsuneji Nagai Award
`
`from the CRS in 2012; the Northeastern University School of Pharmacy
`
`Distinguished Alumni Award in 2016; and Purdue University College of Pharmacy
`
`Distinguished Alumni Award in 2019. Over the course of my career, I have advised
`
`numerous post-doctoral associates, doctoral students, master’s students, visiting
`
`scientists, and research fellows.
`
`14. Over the course of my career, I have been involved in developing
`
`various parenteral and enteral delivery systems. In the area of parenteral
`
`formulations, my research focuses on development of nanoparticulate formulations
`
`of hydrophobic drugs, such as paclitaxel and ceramide, to enhance site-specific
`
`delivery to target tissues and cells. Additionally, my research also focuses on
`
`development of parenteral formulations of biologicals such as peptides, proteins, and
`
`nucleic acid molecules for delivery to specific cells in the body. Indeed, long before
`
`5
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`Declaration of Dr. Mansoor M. Amiji
`
`my involvement with this matter, I published peer reviewed articles in this area. E.g.,
`
`Kaul, G., & Amiji, M. (2005). Tumor-targeted gene delivery using poly(ethylene
`
`glycol)-modified gelatin nanoparticles: in vitro and in vivo studies. Pharmaceutical
`
`research, 22(6), 951–961; Devalapally, H., Chakilam, A., Amiji, M. (2007) Role of
`
`Nanotechnology
`
`in Pharmaceutical Product Development.
`
`Journal of
`
`Pharmaceutical Sciences, 96(10), 2547-2565.
`
`15.
`
`Throughout my career, I have been involved with the design and
`
`development of parenteral systems based on analyzing pharmacokinetic data such
`
`as blood serum or plasma levels of medications and clearance rates. As part of this
`
`work, that would include selection of excipients for such formulations and other
`
`relevant parameters to successfully make parenteral formulations. I have also
`
`published in the area of injectable formulations. For example, I have published an
`
`article entitled Improved oral bioavailability and brain transport of saquinavir upon
`
`administration
`
`in nanoemulsion
`
`formulations
`
`in International Journal of
`
`Pharmaceutics volume 347, pages 93–101 in 2008 where we have developed a lipid
`
`nanoparticle formulation of anti-HIV drug saquinavir and show improvement in oral
`
`bioavailability as well as brain permeability. This study describes both the
`
`formulation development of saquinavir as well as pharmacokinetic evaluations upon
`
`oral administration in rodent models.
`
`6
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`Declaration of Dr. Mansoor M. Amiji
`
`16.
`
`I understand that this matter involves depot formulations. Well before
`
`my involvement with this matter, I have had experience with the design,
`
`development and considerations involved with depot formulations. I have had 15
`
`years cumulative experience with depot formulations, both within the laboratory and
`
`through consulting. I am well versed in this area. Further, in this regard, I have
`
`published articles in the field of depot medications. E.g., Shenoy, D., Little, S.,
`
`Langer, R., & Amiji, M. (2005). Poly(ethylene oxide)-modified poly(beta-amino
`
`ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of
`
`hydrophobic drugs: part 2. In vivo distribution and tumor localization studies.
`
`Pharmaceutical research, 22(12), 2107–2114; Srinivas, G., Devalapally, H.,
`
`Shahiwala A., Amiji, M. (2008). A review of stimuli-responsive nanocarriers for
`
`drug and gene delivery. Journal of Controlled Release, 126, 187-204. My
`
`experience in this area would include selection of excipients for such formulations
`
`as well as parameters involved in their related design.
`
`17.
`
`I have significant expertise in the physicochemical properties of drug
`
`molecules such as pKa, logP and other parameters. I have authored a book Applied
`
`Physical Pharmacy (McGraw-Hill) which is currently in the third edition where
`
`specific chapters on Ionic Equilibria discuss pKa and other physicochemical
`
`properties of drug molecules. This book is specifically used for teaching physical
`
`pharmacy to the undergraduate and PharmD students. Further, in this regard, I have
`
`7
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`Declaration of Dr. Mansoor M. Amiji
`
`published in this area. E.g., Nascimento, A. V., Gattacceca, F., Singh, A., Bousbaa,
`
`H., Ferreira, D., Sarmento, B., & Amiji, M. M. (2016). Biodistribution and
`
`pharmacokinetics of Mad2 siRNA-loaded EGFR-targeted chitosan nanoparticles in
`
`cisplatin sensitive and resistant lung cancer models. Nanomedicine (London,
`
`England), 11(7), 767–781; van Vlerken, L. E., Duan, Z., Little, S. R., Seiden, M. V.,
`
`Amiji, M. M. (2008) Biodistribution and Pharmacokinetic Analysis of Paclitaxel and
`
`Ceramide Administered in Multifunctional Polymer-Blend Nanoparticles in Drug
`
`Resistant Breast Cancer Model. Molecular Pharmaceutics, 5(4), 516-526.
`
`18. Well before my involvement with this matter, I was familiar with
`
`risperidone and reviewed a significant amount of literature on paliperidone.
`
`19. A true and correct copy of my curriculum vitae, which includes a list of
`
`the published papers that I have written, professional honors and memberships, and
`
`presentations that I have given, is attached to this report as EX1027. The matters in
`
`which I have testified in the past four years include:
`
` Reckitt Benckiser Pharmaceuticals, Inc. et al. v. Par Pharmaceutical Inc. et
`al., C.A. No. 1:14-cv-00422-RGA (D. Del.)
`
` Reckitt Benckiser Pharmaceuticals, Inc. et al. v. Watson Laboratories Inc., et
`al., C.A. No. 1:13-cv-01674-RGA (D. Del.)
`
` iCeutica Private, LTD et al. v. Lupin Limited et al., C.A. No. 1:14-cv-01515-
`SLR-SRF (D. Del.)
`
` Mylan Pharmaceuticals Inc. v. Allergan, Inc., No. IPR2016-01127, -1128, -
`1129, -1130, -1131, -1132 (PTAB)
`
`8
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`Mylan v. Janssen (IPR2020-00440) Ex. 1002 p. 012
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`Declaration of Dr. Mansoor M. Amiji
`
` Lipocine, Inc. v. Clarus Therapeutics, Inc., Patent Interference No. 106,045
`(McK)
`
` Cadence Pharmaceuticals Inc., et al. v. InnoPharma Licensing LLC, et al.,
`C.A. No. 1:14-cv-01225-LPS (D. Del.)
`
` Impax Laboratories, Inc. v. Actavis Laboratories FL, Inc. et al., C.A. No.
`2:2015-cv-06934 (D.N.J.)
`
` Reckitt Benckiser LLC v. Aurobindo Pharma Limited, C.A. No. 14-cv-1203-
`LPS (D. Del.)
`
` AMAG Pharmaceuticals, Inc. v. Sandoz, Inc., CA-16-1508-PGS-LHG
`(D.N.J.)
`
` Alcon Research, Ltd. v. Watson Laboratories. Inc., C.A. 16-129-LPS-SRF (D.
`Del.)
`
` Onyx Therapeutics, Inc. v. Cipla Limited, et al., C.A. 16-988-LPS (D. Del)
`
` Almirall, LLC v. Taro Pharmaceutical Industries Ltd., C.A. 17-663-JFB-SRF
`(D. Del.)
`
` Galderma Labs. LP v. Teva Pharmaceuticals USA, Inc., C.A. 17-1783-RGA
`(D. Del.)
`
` FWK Holdings LLC v. Shire PLC et al., CA 16-cv-12653-ADB (Lead) and
`17-cv-10050-ADB (Consol.) (D. Mass.)
`
` Impax Laboratories, Inc., v. Zydus Pharmaceuticals Inc & Cadilla
`Healthcare, 17-cv-13476 (SRC)(CLW) (D, NJ)
`
`3.
`
`LIST OF MATERIALS CONSIDERED
`
`20.
`
`I have reviewed the ’906 patent, the prosecution history, and each of
`
`the documents cited herein, in consideration of general knowledge in the art as of
`
`December 5, 2008. In forming my opinions, I have relied upon my experience in the
`
`9
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`Declaration of Dr. Mansoor M. Amiji
`
`relevant art. I have also considered the viewpoint of a POSA as defined below as of
`
`December 2008. I have considered all documents cited in this Declaration and all
`
`documents cited in the Petition for Inter Partes Review of the ’906 patent, as well
`
`as the following documents:
`
`Exhibit #
`
`Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`1006
`
`1007
`
`1008
`1009
`
`1010
`
`U.S. Patent No. 9,439,906 (“the ’906 patent”)
`
`N/A
`
`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”)
`
`10
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`Declaration of Dr. Mansoor M. Amiji
`
`Exhibit #
`
`Description
`
`1011
`
`1012
`
`1013
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`1024
`
`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”)
`
`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”)
`
`11
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`Declaration of Dr. Mansoor M. Amiji
`
`Exhibit #
`
`Description
`
`1025
`1026
`1027
`1028
`
`1029
`
`1030
`1031
`
`1032
`
`1033
`
`1034
`
`Orange Book Entry for Invega Sustenna®
`
`Excerpt of ’906 Patent Prosecution History (“11-11-2015 IDS”)
`
`Curriculum Vitae of Dr. Mansoor Amiji
`
`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”)
`
`12
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`Mylan v. Janssen (IPR2020-00440) Ex. 1002 p. 016
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`

`

`Declaration of Dr. Mansoor M. Amiji
`
`Description
`
`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”)
`
`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
`
`Exhibit #
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`13
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`Mylan v. Janssen (IPR2020-00440) Ex. 1002 p. 017
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`

`

`Declaration of Dr. Mansoor M. Amiji
`
`Exhibit #
`
`1046
`
`Description
`
`Janicak, Philip G., and Elizabeth A. Winans. Paliperidone ER: a
`review of the clinical trial data. Neuropsychiatric disease and
`treatment 3.6 (2007):869
`
`1047
`
`Physicians’ Desk Reference (2002), HALDOL® Decanoate
`
`4.
`
`LEGAL STANDARD
`
`21. Although I am not a lawyer, I have been informed by counsel and
`
`provide my general understanding of the law of obviousness. I used these principles
`
`in conducting my analysis and drawing any conclusions.
`
`22.
`
`I understand that the first step in determining whether a patent claim
`
`would have been obvious is to construe the claims to determine claim scope and
`
`meaning. I understand that in IPR proceedings, the claims must generally be given
`
`“the meaning that the term would have to a person of ordinary skill in the art in
`
`question at the time of the invention.”
`
`A.
`
`23.
`
`Obviousness
`
`I understand that a patent claim is invalid if the differences between the
`
`claimed invention and prior art are such that the subject matter as a whole would
`
`have been obvious at the time the invention was made to a POSA.
`
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`Declaration of Dr. Mansoor M. Amiji
`
`24.
`
`I have been told the following factors (sometimes referred to as the
`
`Graham factors) are used in making an obviousness determination: a) the scope and
`
`content of the prior art; b) the differences between the prior art and the claimed
`
`invention; c) the level of ordinary skill in the pertinent art; and d) any secondary
`
`considerations evidencing non-obviousness. The obviousness analysis looks to the
`
`state of the art that existed at the time the invention was made.
`
`25. Moreover, obviousness does not require absolute predictability of
`
`success; all that is required is a reasonable expectation of success. I have been
`
`informed that the person of ordinary skill need only have a reasonable expectation
`
`of success of developing the claimed invention. Another helpful formulation of this
`
`concept is to ask whether or not a skilled artisan would have perceived a reasonable
`
`expectation of success in making the invention in light of the prior art.
`
`26.
`
`Finally, obviousness cannot be avoided simply by a showing of some
`
`degree of unpredictability in the art so long as there was a reasonable probability of
`
`success.
`
`27.
`
`I also understand that obviousness can be established by combining or
`
`modifying the teachings of the prior art. A claimed invention can be obvious when,
`
`for example, there is some teaching, suggestion, or motivation in the prior art that
`
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`Declaration of Dr. Mansoor M. Amiji
`
`would have led a POSA to modify the prior art reference or to combine prior art
`
`reference teachings to arrive at the claimed invention.2
`
`28.
`
`I also understand that the prior art references themselves do not have to
`
`provide an explicit teaching, suggestion, or motivation to combine prior art
`
`teachings; rather, the analysis may rely on interrelated teachings, market demands,
`
`the background knowledge possessed by a POSA, and/or common sense. A POSA
`
`can also take account of the inferences and creative steps that he or she would
`
`employ including fitting various pieces of prior art together like a jigsaw puzzle. Put
`
`another way, the motivation to combine or modify prior art references can come
`
`from any reason to do so and is not limited to the reasons that may have motivated
`
`the patentee.
`
`29.
`
`I am also informed that a combination of familiar elements according
`
`to known methods is likely to be obvious when it does no more than yield predictable
`
`results. I also understand that when a POSA would have reached the claimed
`
`invention through routine experimentation, the invention may be deemed obvious.
`
`2 As a general matter, in my view, in science and technology, a POSA would
`
`not view any single disclosure as complete, and thus, look no further. Were that the
`
`case, society would have halted progress long ago. Instead, ordinary artisans always
`
`seek improvement in their respective fields.
`
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`Declaration of Dr. Mansoor M. Amiji
`
`30.
`
`I understand that various rationales are utilized to determine whether a
`
`claim
`
`is obvious,
`
`including, among others:
`
` (i) simple substitution or
`
`interchangeability of one known element for another to obtain predictable results;
`
`(ii) use of known techniques to improve similar methods or products in the same
`
`way; (iii) applying a known technique to a known method or product ready for
`
`improvement to yield predictable results; (iv) “obvious to try”—choosing from a
`
`finite number of identified, predictable solutions, with a reasonable expectation of
`
`success; and (v) known work in one field of endeavor prompting variations of it for
`
`use in either the same field or a different one based on design incentives or other
`
`market forces if the variations would have been predictable to one of ordinary skill
`
`in the art.
`
`31. As stated above, I understand that secondary considerations of non-
`
`obviousness are part of the obviousness inquiry. I understand that these secondary
`
`considerations may include failure of others, copying, unexpectedly superior results,
`
`perception in the industry, commercial success, and long-felt but unmet need. I also
`
`understand that for secondary considerations of non-obviousness to be applicable,
`
`they must have a nexus to the claimed subject matter. I understand that this nexus
`
`(i.e., link) includes a connection between the subject matter of the claim and the
`
`alleged secondary considerations.
`
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`Declaration of Dr. Mansoor M. Amiji
`
`32.
`
`I understand that I cannot use hindsight in any obviousness analysis. In
`
`connection with my opinions, I did not use hindsight, nor did I use the claims and/or
`
`the disclosure of the ’906 patent as a blueprint for piecing together the prior art to
`
`arrive at the claimed invention. As part of the obviousness analysis, and to avoid
`
`hindsight, I thought back to the time of invention (i.e., the relevant priority date
`
`(discussed further below)) and considered the thinking of a POSA, guided only by
`
`the prior art references and the then-accepted wisdom in the field.
`
`5.
`
`PERSON OF ORDINARY