UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`HIKMA PHARMACEUTICALS USA INC.,
`HIKMA PHARMACEUTICALS PLC,
`Petitioner,
`
`v.
`
`AMARIN PHARMACEUTICALS IRELAND LIMITED,
`Patent Owner.
`
`Case IPR2021-00215
`Patent 8,642,077 B2
`Issued: February 4, 2014
`
`Title: STABLE PHARMACEUTICAL
`COMPOSITION AND METHODS OF USING SAME
`
`DECLARATION OF EDWARD A. FISHER, M.D., Ph.D., M.P.H.
`
`Hikma Pharmaceuticals
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`IPR2022-00215
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`Ex. 1002, p. 1 of 92
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`

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`IPR2021-00215 (8,642,077 B2)
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`TABLE OF CONTENTS
`
`LIST OF CITED EXHIBITS ................................................................................... iii
`I.
`INTRODUCTION ........................................................................................... 7
`II.
`BACKGROUND AND QUALIFICATIONS.................................................. 8
`III. LEGAL STANDARDS USED IN MY ANALYSIS ..................................... 13
`A.
`Prior art ................................................................................................ 14
`B.
`Person of ordinary skill in the art ........................................................ 14
`C.
`Anticipation ......................................................................................... 16
`D. Obviousness ......................................................................................... 17
`IV. THE ʼ077 PATENT ........................................................................................ 20
`A.
`The challenged claims ......................................................................... 20
`B.
`The specification ................................................................................. 21
`TECHNICAL BACKGROUND ................................................................... 23
`V.
`VI. CLAIM CONSTRUCTION .......................................................................... 26
`VII. PRIOR-ART REFERENCES ........................................................................ 31
`A. Yokoyama I ......................................................................................... 31
`B. Mori ..................................................................................................... 34
`C.
`Yokoyama II ........................................................................................ 35
`D.
`Satoh .................................................................................................... 37
`E.
`Grimsgaard .......................................................................................... 40
`VIII. OPINIONS OF UNPATENTABILITY ......................................................... 41
`A. Grounds based on Yokoyama I ............................................................ 42
`1.
`Ground A.1: Yokoyama I anticipates claims 1, 8, and 19. ........ 42
`a.
`Independent claim 1 ........................................................ 42
`b.
`Dependent claim 8 .......................................................... 52
`c.
`Dependent claim 19 ........................................................ 56
`Ground A.2: Dependent claim 8 would have been obvious over
`Yokoyama I in view of Satoh. .................................................. 56
`Ground A.3: Dependent claims 14–18 would have been obvious
`over Yokoyama I in view of Grimsgaard. ................................ 60
`
`3.
`
`2.
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`IPR2021-00215 (8,642,077 B2)
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`B.
`
`a.
`Dependent claims 14, 16, 17 .......................................... 60
`Dependent claims 15 and 18 ........................................... 63
`b.
`Grounds based on Mori and Yokoyama II .......................................... 63
`1.
`Ground B.1: Claims 1, 8, and 19 would have been obvious over
`Mori in view of Yokoyama II. .................................................. 64
`a.
`Independent claim 1 ........................................................ 64
`b.
`Dependent claim 8 .......................................................... 71
`c.
`Dependent claim 19 ........................................................ 72
`Ground B.2: Dependent claim 8 would have been obvious over
`Mori in view of Yokoyama II and Satoh. ................................. 73
`Ground B.3: Dependent claims 14–18 would have been obvious
`over Mori in view of Yokoyama II and Grimsgaard. ............... 74
`a.
`Dependent claims 14, 16, 17 .......................................... 74
`b.
`Dependent claims 15 and 18 ........................................... 76
`There are no secondary considerations of nonobviousness. ............... 77
`1.
`The claimed method does not produce unexpected results. ..... 77
`2.
`Patent Owner’s Vascepa lacks a nexus to the claims. .............. 86
`3.
`Any alleged secondary considerations would be discounted by
`the blocking effect of existing and expected patents. ............... 87
`IX. CONCLUSION .............................................................................................. 90
`
`
`2.
`
`3.
`
`C.
`
`
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`IPR2021-00215 (8,642,077 B2)
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`LIST OF CITED EXHIBITS
`
`Description
`U.S. Patent No. 8,642,077 B2 to Manku et al. (the “ʼ077 patent”)
`Expert Declaration of Edward A. Fisher, M.D., Ph.D., M.P.H.
`WO 2007/142118 to Yokoyama et al. (2007) (certified English
`translation) (“Yokoyama I”)
`Trevor A. Mori et al., Purified Eicosapentaenoic and
`Docosahexaenoic Acids Have Differential Effects on Serum Lipids
`and Lipoproteins, LDL Particle Size, Glucose, and Insulin in Mildly
`Hyperlipidemic Men, 71 AM. J. CLINICAL NUTRI. 1085 (2000)
`(“Mori”)
`Mitsuhiro Yokoyama et al., Effects of Eicosapentaenoic Acid on
`Major Coronary Events in Hypercholesterolaemic Patients (JELIS):
`a Randomized Open- Label, Blinded Endpoint Analysis, 369
`LANCET 1090 (2007) (“Yokoyama II”)
`Noriko Satoh et al., Purified Eicosapentaenoic Acid Reduces Small
`Dense LDL, Remnant Lipoprotein Particles, and C-Reactive Protein
`in Metabolic Syndrome, 30 DIABETES CARE 144 (2007) (“Satoh”)
`Sameline Grimsgaard et al., Highly Purified Eicosapentaenoic Acid
`and Docosahexaenoic Acid in Humans Have Similar
`Triacylglycerol-Lowering Effects but Divergent Effects on Serum
`Fatty Acids, 66 AM. J. CLINICAL NUTRI. 649 (1997) (“Grimsgaard”)
`Third Report of the National Cholesterol Education Program
`(NCEP) Expert Panel on Detection, Evaluation, and Treatment of
`High Blood Cholesterol in Adults (Adult Treatment Panel 111)
`Final Report, 106 CIRCULATION 3143 (2002) (“ATP-III”)
`Plaintiffs’ Corrected Post-Trial Proposed Findings of Fact and
`Conclusions of Law (Feb. 27, 2020) from Amarin Pharma, Inc. v.
`Hikma Pharm. USA Inc., No. 16-2525, D.I. 377, ¶ 510 (D. Nev.)
`(“Amarin FFCL”)
`Day 2 (Jan. 14, 2020) Trial Transcript from Amarin Pharma, Inc. v.
`Hikma Pharm. USA Inc., No. 16-2525 (D. Nev.) (Testimony of Dr.
`Budoff) (“Bufoff Tr.”)
`Margaret Carroll, et al., Serum Lipids of Adults 20–74 Years: United
`States, 1976–80, Nat’l Ctr for Health Statistics, Vital & Health
`Statistics, 11(242) (1993) (“Nat’l Health Survey”)
`
`No.
`1001
`1002
`1003
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
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`No.
`1012
`
`1014
`
`1015
`
`1016
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`IPR2021-00215 (8,642,077 B2)
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`Description
`Hartmut H-J Schmidt et al., Lipid Evaluation in HIV-1-Positive
`Patients Treated with Protease Inhibitors, 4 ANTIVIRAL THER. 163
`(1999) (“Schmidt”)
`Lovaza®, PHYSICIANS’ DESK REFERENCE 2699 (62d ed. 2007)
`(“Lovaza PDR”)
`Shuichi Nozaki et al., Effects of Purified Eicosapentaenoic Acid
`Ethyl Ester on Plasma Lipoproteins in Primary
`Hypercholesterolemia, 62 INT’L J. VITAMIN & NUTR. RES.
`256(1992) (“Nozaki”)
`Koji Shinozaki et al., The Long-Term Effect of Eicosapentaenoic
`Acid on Serum Levels of Lipoprotein (a) and Lipids in Patients with
`Vascular Disease, 2(2) J. ATHEROSCL. THROMB. 107 (1996)
`(“Shinozaki”)
`Day 7 (Jan. 28, 2020) Trial Transcript from Amarin Pharma, Inc. v.
`Hikma Pharm. USA Inc., No. 16-2525 (D. Nev.) (Testimony of Dr.
`Toth) (“Toth Tr.”)
`Plaintiffs’ Validity Contentions from Amarin Pharma, Inc. v. Hikma
`Pharm. USA Inc., No. 16-2525 (D. Nev.)
`Plaintiffs’ Infringement Contentions from Amarin Pharma, Inc. et
`al. v. Hikma Pharm. USA Inc. et al., C.A. No. 20-1630 (D. Del.)
`Plaintiffs’ Opposition to Motion to Dismiss from Amarin Pharma,
`Inc. et al. v. Hikma Pharm. USA Inc. et al., C.A. No. 20-1630 (D.
`Del.)
`Plaintiffs’ First Amended Complaint from Amarin Pharma, Inc. et
`al. v. Hikma Pharm. USA Inc. et al., C.A. No. 20-1630, D.I. 17 (D.
`Del.) (“Complaint”)
`Exhibit U to Plaintiffs’ First Amended Complaint from Amarin
`Pharma, Inc. et al. v. Hikma Pharm. USA Inc. et al., C.A. No. 20-
`1630, D.I. 17-22 (D. Del.) (Christie Ballantyne et al., Efficacy and
`Safety of Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in
`Statin-Treated Patients with Persistent High Triglycerides, AM. J.
`CARDIOL. 1 (2012)) (“Ballantyne”)
`Exhibit V to Plaintiffs’ First Amended Complaint from Amarin
`Pharma, Inc. et al. v. Hikma Pharm. USA Inc. et al., C.A. No. 20-
`1630, D.I. 17-23 (D. Del.) (Deepak L. Bhatt et al., Cardiovascular
`Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia, 380
`N. ENGL. J. MED. 11 (2018)) (“Bhatt”)
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`No.
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`1034
`
`1035
`
`1039
`1040
`1041
`1042
`1043
`
`Description
`Amarin Response to U.S. Patent Office re U.S. Patent Application
`No. 13/768,906 (Aug. 26, 2013)
`Michael H. Davidson et al., Efficacy and Tolerability of Adding
`Prescription Omega-3 Fatty Acids 4 g/d to Simvastatin 40 mg/d in
`Hypertriglyceridemic Patients: An 8-Week, Randomized, Double-
`Blind, Placebo-Controlled Study, 29 CLIN. THERAPEUTICS 1354
`(2007) (“Davidson”)
`Yasushi Saito et al., Effects of EPA on Coronary Artery Disease in
`Hypercholesterolemic Patients with Multiple Risk Factors: Sub-
`Analysis of Primary Prevention Cases from the Japan EPA Lipid
`Intervention Study (JELIS), 200 ATHEROSCLEROSIS 135 (2008)
`(“Saito”)
`Notice of Allowability from U.S. Patent Office re U.S. Patent
`Application No. 13/768,906 (Sept. 30, 2013)
`FDA Briefing Document, Endocrinologic and Metabolic Drugs,
`Advisory Committee Meeting regarding ANCHOR trial (Oct. 16,
`2013)
`U.S. Patent Office Interview Summary re U.S. Patent Application
`No. 13/614,111 (Dec. 12, 2012)
`Amarin Supplemental Response to U.S. Patent Office re U.S. Patent
`Application No. 13/614,111 (Jan. 11, 2013)
`Notice of Allowability from U.S. Patent Office re U.S. Patent
`Application No. 13/614,111 (Feb. 11, 2013)
`Vascepa® Label (rev. Dec. 2019)
`World Health Organization Memorandum, Classification of
`Hyperlipoproteinemias and Hyperlipoproteinemias, 43
`CIRCULATION 501 (1972) (“WHO Memo”)
`Declaration of C. Rosebraugh from Amarin Pharma, Inc. et al. v.
`U.S. F.D.A. et al., No. 15-3588, D.I. 54 (S.D.N.Y.)
`Original Japanese version of WO 2007/142118 to Yokoyama et al.
`U.S. Patent No. 6,384,077 to Peet et al.
`U.S. Patent No. 6,479,544 to Horrobin
`U.S. Patent No. 7,119,118 to Peet et al.
`Amarin Reports Fourth Quarter and Full Year 2004 Results Report
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`IPR2021-00215 (8,642,077 B2)
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`No.
`1044
`
`1045
`
`1046
`
`1047
`1048
`1049
`
`Description
`U.S. Patent Application Publication No. 2007/0021504 A1 to
`Yokoyama et al.
`Yokoyama et al., Effects of eicosapentaenoic acid on
`cardiovascular events in Japanese patients with
`hypercholesterolemia: Rationale, design, and baseline
`characteristics of the Japan EPA Lipid Intervention Study (JELIS),
`146 Am. Heart J. 613-20 (2003)
`Joint Claim Construction Chart from Amarin Pharma, Inc. et al. v.
`Hikma Pharm. USA Inc. et al., C.A. No. 20-1630, D.I. 94 (D. Del.)
`Curriculum vitae of Edward A. Fisher
`Lipitor® (atorvastatin calcium) tablets, labeling (rev. Sept. 2007)
`Crestor® (rosuvastatin calcium) tablets, labeling (rev. Nov. 2007)
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`IPR2021-00215 (8,642,077 B2)
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`I, Edward A. Fisher, M.D., Ph.D., M.P.H, declare as follows:
`
`I.
`
`INTRODUCTION
`1.
`I have been retained by Hikma Pharmaceuticals USA Inc. and Hikma
`
`Pharmaceuticals PLC (collectively, “Petitioner”) in connection with their request
`
`for inter partes review of U.S. Patent No. 8,642,077 (“the ’077 patent”). A copy of
`
`the ’077 patent has been marked Ex. 1001. I have reviewed and am familiar with
`
`the ’077 patent, which generally relates to a method of reducing triglycerides in a
`
`subject with mixed dyslipidemia on statin therapy by administering a purified form
`
`of eicosapentaeonic acid (“EPA”), which, along with docosahexaenoic acid
`
`(“DHA”), is an omega-3 fatty acid found naturally in fish oil.
`
`2.
`
`I have been asked to provide my opinions regarding the patentability
`
`of claims 1, 8, and 14–19 of the ’077 patent (the “challenged claims”). This
`
`declaration discusses my background and qualifications, the legal standards used in
`
`my analysis, an overview of the ʼ077 patent from the perspective of a person of
`
`ordinary skill in the art as of the patent’s earliest filing date (a “POSA”), and my
`
`opinions regarding the patentability of the challenged claims.
`
`3. My work in this proceeding is being charged to Petitioner at a
`
`standard rate of $1,050 per hour. My compensation is in no way contingent on the
`
`substance of my opinions or the outcome of this proceeding.
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`4.
`
`As set forth more fully below, it is my opinion that the challenged
`
`claims of the ’077 patent are unpatentable under the following grounds:
`
`Ground Claims
`
`Basis
`
`Reference(s)
`
`A.1
`
`A.2
`
`A.3
`
`B.1
`
`B.2
`
`1, 8, 19 Anticipation Yokoyama I (Ex. 1003)
`
`8
`
`Obviousness Yokoyama I (Ex. 1003), Satoh (Ex. 1006)
`
`14–18 Obviousness Yokoyama I (Ex. 1003),
`
`Grimsgaard (Ex. 1007)
`
`1, 8, 19 Obviousness Mori (Ex. 1004), Yokoyama II (Ex. 1005)
`
`8
`
`Obviousness Mori (Ex. 1004), Yokoyama II (Ex. 1005),
`
`Satoh (Ex. 1006)
`
`B.3
`
`14–18 Obviousness Mori (Ex. 1004), Yokoyama II (Ex. 1005),
`
`Grimsgaard (Ex. 1007)
`
`
`The bases for my opinions are set forth in this declaration.
`
`II. BACKGROUND AND QUALIFICATIONS
`5.
`I am currently the Leon H. Charney Professor of Cardiovascular
`
`Medicine, and Professor in the Departments of Medicine (Cardiology), Pediatrics
`
`and Cell Biology at the New York University School of Medicine. I have been
`
`with the faculty at the New York University School of Medicine since 2003. I am
`
`also a Visiting Professor for the Department of Cardiovascular Medicine at the
`
`University of Oxford since 2010. At NYU, I direct the vascular biology research
`
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`program and am a member, and former director, of the Center for the Prevention of
`
`Cardiovascular Disease. My complete educational background, professional
`
`experience, and qualifications are set forth in my curriculum vitae, which is
`
`Exhibit 1047. Below is a summary of several of my relevant qualifications.
`
`6.
`
`I received my B.A. at Harpur College, State University of New York,
`
`in 1971. In 1975, I received my M.D. from New York University School of
`
`Medicine, and in 1978, I received my Masters in Public Health from the University
`
`of North Carolina. From 1975–1977, I was a resident physician at Duke
`
`University. From 1978–1981, I did fellowships at the Children’s Hospital (affiliate
`
`of Harvard Medical School) and the Clinical Research Center at Massachusetts
`
`Institute of Technology (“MIT”) while working toward my Ph.D., which I received
`
`in 1982 from MIT in biochemistry and nutrition under the direction of Professor
`
`Jan Breslow. My thesis at MIT focused on apolipoprotein E metabolism. I was a
`
`Medical Staff Fellow in Human Genetics at the National Institutes of Health from
`
`1981–1984. In 2010, I received my M.A. from the University of Oxford.
`
`7.
`
`Since graduate school, my research has focused on the cell biology of
`
`hepatic lipid and lipoprotein metabolism and the molecular biology of vascular
`
`diseases, including the progression and regression of atherosclerotic plaques. My
`
`current research focuses on the regression of plaques after the normalization of
`
`hyperlipidemia and the effects of high-density lipoproteins (“HDL”) on plaque
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`progression and regression, as well as the secretion of very-low-density
`
`lipoproteins (“VLDL”) by the liver, which are the precursors of low-density
`
`lipoproteins (“LDL”).
`
`8.
`
`For the last 26 years, I have frequently received funding for my
`
`research from the NHLBI, NIH, American Heart Association, and Department of
`
`Defense. My research has related to lipoprotein metabolism (including the effects
`
`of EPA and DHA) and atherosclerosis (including on the regression of plaques in
`
`the arteries of the type that cause heart attacks). I am, or have been, a member of
`
`the scientific advisory boards of a number of organizations focused on lipid
`
`management in diabetic and non-diabetic patients, including the NIH, the
`
`Cardiovascular Research Institute of the University of Rochester, the American
`
`Heart Association Nutrition Committee, the Takeda Advisory Board on Diabetes,
`
`and the Merck Global Advisory Board in Atherosclerosis.
`
`9.
`
`As a professor, I have supervised more than seven graduate student
`
`Ph.D. theses and mentored more than 60 postdoctoral scholars. I have supervised
`
`and directed the work of students and scholars in the fields of lipoprotein
`
`metabolism and atherosclerosis.
`
`10.
`
`I have received numerous awards and honors for my research in
`
`lipoprotein metabolism and the molecular biology of vascular diseases, including
`
`atherosclerosis and other diseases related to cholesterol buildup. Among other
`
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`honors, I received the Solomon A. Berson Award for Basic Science Achievement
`
`from the NYU School of Medicine, Distinguished Achievement Award from the
`
`American Heart Association, and the Lifetime Achievement Award from the
`
`National Lipid Association for “extraordinary contributions to the field of
`
`lipidology.” I was elected to the American Association of Physicians in 2009 and
`
`the Association of University Cardiologists in 2012. I also presented the Frank
`
`Tyler Honorary Endowed Lecture at the University of Utah School of Medicine on
`
`the regression of atherosclerosis and the George Lynman Duff Lecture at the
`
`American Heart Association Annual Scientific Sessions on lipoprotein metabolism,
`
`atherosclerosis regression, and nanotherapies. In 2010–2011, I was the George
`
`Eastman Professor at Oxford University, an honor shared with 13 Nobel laureates.
`
`11.
`
`I have authored or co-authored more than 350 published articles and
`
`numerous book chapters in the fields of lipoprotein metabolism, vascular biology,
`
`atherosclerosis, and preventive cardiology. I have given numerous lectures world-
`
`wide on these topics, particularly in the fields of lipoprotein metabolism and
`
`atherosclerosis.
`
`12.
`
`I currently serve on the Editorial Boards of the Journal of Clinical
`
`Investigation, the Journal of Lipid Research, and Circulation Research. I have also
`
`served on the Editorial Boards of the Journal of the American College of Nutrition,
`
`and the Journal of Biological Chemistry. I was Associate Editor, then Editor-in-
`
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`Chief, of Arteriosclerosis, Thrombosis, Vascular Biology (an American Heart
`
`Association journal) from 2007–2011. I currently serve on the Advisory Board for
`
`the University of Rochester Medical Center Cardiovascular Research Institute. I
`
`also served on Advisory Boards for several universities and corporations. I have
`
`also served as a consultant for numerous biotechnology and pharmaceutical
`
`companies on matters relating to lipoprotein metabolism, atherosclerosis, and
`
`preventive cardiology.
`
`13.
`
`I am a member of a number of professional organizations and
`
`societies, including the American Heart Association and the National Lipid
`
`Association. I am also a Fellow of the American Heart Association and a Fellow
`
`of its Council on Arteriosclerosis, Thrombosis, and Vascular Biology. I also
`
`served on the Board of Directors of the National Lipid Association (Northeast
`
`section) from 2007–2009.
`
`14.
`
`I am an active practitioner in the area of preventive cardiology, with
`
`particular clinical expertise in managing patients with high cholesterol and
`
`triglyceride levels. I am also the founding director of the Center for the Prevention
`
`of Cardiovascular Disease at the NYU Medical Center. For the first seven years of
`
`this Prevention Center (2003–2010), I personally saw hundreds of patients with
`
`various lipid disorders, including familial hypercholesterolemia, chylomicronemia,
`
`and hypertriglyceridemia. I treated these patients with various types of lipid-
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`lowering medications, including statins, fibrates, niacin, Lovaza (omega-3 ethyl
`
`esters), and nutritional fish oil supplements. Had Vascepa (icosapent ethyl) been
`
`approved at the time I was seeing patients in my clinical practice, I would have
`
`considered prescribing Vascepa as well.
`
`15. As the NYU Center for the Prevention of Cardiovascular Disease
`
`expanded (we currently have six other preventive cardiologists besides myself), I
`
`gave up seeing patients on a daily basis and took on a consulting role. I have also
`
`spent more time on administrative and fundraising activities. Currently, my
`
`clinical activities involve serving as an in-patient attending physician in preventive
`
`cardiology at the Center. In this role, for nine weeks a year, I see approximately
`
`10–20 patients each week who have been admitted to the hospital for invasive
`
`cardiovascular procedures, such as catheterization, angioplasty, and stenting. Most
`
`of these patients have cholesterol or triglyceride abnormalities, including familial
`
`hypercholesterolemia, and I make recommendations to their referring physicians
`
`for the treatment of the lipid disorders.
`
`III. LEGAL STANDARDS USED IN MY ANALYSIS
`16.
`I am not a patent attorney, nor have I independently researched patent
`
`law. Counsel for Petitioner have explained certain legal standards to me that I
`
`have relied upon in forming my opinions set forth in this Declaration. I set forth
`
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`some of these legal standards below and set forth additional legal standards in my
`
`analysis in later sections of this Declaration.
`
`A.
`17.
`
`Prior art
`I have been informed that the law provides certain categories of
`
`information, known as prior art, that may be used to render patent claims
`
`anticipated or obvious. I understand that the reference materials I discuss in this
`
`declaration are prior art at least because they would have been available to
`
`members of the public as of April 29, 2009, and are relevant to the subject matter
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`of the ʼ077 patent. The references I discuss are from the same field of endeavor as
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`the claimed invention (even if they address a different problem) and/or are
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`reasonably pertinent to the problem faced by the named inventors (even if they are
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`not in the same field of endeavor as the claimed invention).
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`B.
`18.
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`Person of ordinary skill in the art
`I understand that the ’077 patent claims priority to U.S. Provisional
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`Application No. 61/173,763, which was filed on April 29, 2009, as stated on the
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`cover of the ’077 patent in item “(60)” under the title “Related U.S. Application
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`Data.” For purposes of my analysis, and without offering any opinion as to
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`whether the ʼ077 patent’s claim to priority is valid or appropriate, I have used the
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`April 29, 2009, date as the relevant date for my analysis of the prior art. My
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`opinions set forth in this Declaration would not change, however, if the relevant
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`IPR2022-00215
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`Ex. 1002, p. 15 of 92
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`IPR2021-00215 (8,642,077 B2)
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`date were one year prior to this priority date—i.e., April 29, 2008—which I
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`understand is the earliest critical date for the ’077 patent.
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`19.
`
`I understand that the assessment of the patentability of the claims of
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`the ’077 patent must be undertaken from the perspective of a hypothetical POSA as
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`of the priority date of the ’077 patent. I understand that the POSA is a hypothetical
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`person who is presumed to have known all the relevant art as of the priority date. I
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`understand factors that may be considered in determining the level of ordinary skill
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`of a POSA include (i) the types of problems encountered in the art, (ii) prior art
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`solutions to those problems, (iii) rapidity with which innovations are made, (iv)
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`sophistication of the technology, and (v) educational level of active workers in the
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`field. I understand that in a given case, every factor may not be present, and one or
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`more factors may predominate.
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`20.
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`I understand that the hypothetical POSA to which the claimed subject
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`matter pertains would have had the capability of understanding the scientific and
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`medical principles applicable to the pertinent art. I further understand that a POSA
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`is also a person of ordinary creativity, not an automaton.
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`21. Based on these factors, my knowledge and expertise, and the prior art
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`to the ’077 patent (i.e., publications available before April 29, 2009), it is my
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`opinion that a POSA at the time of the relevant priority date would have had (1) a
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`medical degree; (2) several years of experience in the development and/or clinical
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`IPR2022-00215
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`Ex. 1002, p. 16 of 92
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`use of fatty acids to treat cardiovascular, endocrine, and/or lipid disorders,
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`including fish-oil-based fatty acids, i.e., EPA and/or DHA, and their dosage forms;
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`and (3) access to a team including one or more of an analytical chemist,
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`pharmaceutical chemist, formulator, or biostatistician.
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`22.
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`I meet this definition of a POSA today and met this definition at all
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`times between April 2008 and April 2009.
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`C. Anticipation
`23.
`I have been informed that a claim is anticipated if each and every
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`limitation of the claim is found either expressly or inherently in a single prior art
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`reference. I have been informed that anticipation does not require the actual
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`creation or reduction to practice of the prior art subject matter; anticipation
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`requires only an enabling disclosure. I have also been informed that the
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`anticipation analysis asks solely whether the prior art reference discloses and
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`enables the claimed invention, and not how the prior art characterizes that
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`disclosure or whether alternatives are also disclosed.
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`24.
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`I have been informed that a reference can anticipate a claim even if it
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`does not expressly spell out all the limitations arranged or combined as in the
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`claim, if a POSA, reading the reference, would at once envisage the claimed
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`arrangement or combination.
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`Ex. 1002, p. 17 of 92
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`25.
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`I have been informed that a prior art reference may anticipate without
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`disclosing a feature of the claimed invention if that missing characteristic is
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`necessarily present, or inherent, in the single anticipating reference. I have been
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`informed that, under the principle of inherency, if the prior art necessarily
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`functions in accordance with, or includes, the claimed limitations, it anticipates.
`
`D. Obviousness
`26.
`I have been informed that, even if every element of a claim is not
`
`found explicitly or implicitly in a single prior art reference, the claim may still be
`
`unpatentable if the differences between the claim and the prior art are such that the
`
`claim as a whole would have been obvious to a POSA at the time the invention
`
`was made. For purposes of obviousness, I understand that a POSA may rely on a
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`single prior art reference or multiple references in combination.
`
`27.
`
`I have been informed that the following four factors are considered
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`when determining whether a patent claim would have been obvious to a POSA: (a)
`
`the level of ordinary skill in the art; (b) the scope and content of the prior art; (c)
`
`the differences between the prior art and the claim; and (d) any “secondary
`
`considerations” tending to prove nonobviousness. These secondary considerations,
`
`which I understand are also called “objective indicia” or “objective evidence,” may
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`include factors such as: (i) the invention’s satisfaction of a long-felt unmet need in
`
`the art; (ii) unexpected results of the invention; (iii) skepticism of the invention by
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`Ex. 1002, p. 18 of 92
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`IPR2021-00215 (8,642,077 B2)
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`experts; (iv) commercial success of an embodiment of the invention; and (vii)
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`praise by others for the invention. I have also been informed that there must be an
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`adequate nexus or connection between the evidence that is the basis for an asserted
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`secondary consideration and the scope of the invention claimed in the patent.
`
`28.
`
`I understand that when every limitation of a claim is disclosed in the
`
`cited prior art references, the question of obviousness turns on whether a
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`hypothetical person of ordinary skill in the art would have been motivated to
`
`combine those teachings to derive the claimed subject matter with a reasonable
`
`expectation of success. Further, I understand that obviousness does not require
`
`absolute predictability. Only a reasonable expectation that the beneficial result
`
`will be achieved is necessary to show obviousness.
`
`29.
`
`I have been informed that a claimed invention can be rendered
`
`obvious by the combination of teachings in the prior art even if there is no explicit
`
`teaching to combine them. Instead, any problem known in the field at the time of
`
`the alleged invention can provide a sufficient rationale to combine the elements of
`
`the prior art in the manner claimed in the patent.
`
`30.
`
`I have been informed that examples of sufficient rationales for
`
`establishing obviousness include the following:
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`• combining prior art elements according to known methods to yield
`
`predictable results;
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`IPR2022-00215
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`Ex. 1002, p. 19 of 92
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`• substituting known elements for other known elements to obtain
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`predictable results;
`
`• using a known technique to improve similar devices, methods, or
`
`products in the same way;
`
`• choosing from a finite number of identified, predictable solutions that
`
`would be obvious to try; and
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`• providing some teaching, suggestion, or motivation to modify the
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`prior art reference or to combine teachings in prior art references to
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`arrive at the claimed invention.
`
`31.
`
`I understand that where there is a range disclosed in the prior art, and
`
`the claimed invention falls within that range, the burden of production falls upon
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`the patentee to come forward with evidence that (1) the prior art taught away from
`
`the claimed invention; (2) there were new and unexpected results relative to the
`
`prior art; or (3) there are other pertinent secondary considerations. For purposes of
`
`this analysis, I understand that a prior art reference “teaches away” from a claimed
`
`invention if it criticizes, discredits, or otherwise discourages investigation into the
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`invention claimed.
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`-19-
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`IPR2022-00215
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`Ex. 1002, p. 20 of 92
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`IPR2021-00215 (8,642,077 B2)
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`IV. THE ʼ077 PATENT
`A. The challenged claims
`32. The ’077 patent generally relates to compositions containing EPA and
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`methods of using such compositions to treat patients. Ex. 1001 at 1:1–3, 1:41–59.
`
`Claim 1 is the sole independent claim of the ’077 patent:
`
`1. A method of reducing triglycerides in a subject with mixed
`dyslipidemia on statin therapy comprising, administering to the
`subject a pharmaceutical composition comprising about 2500 mg to
`5000 mg