UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`APOTEX INC.
`Petitioners
`
`v.
`
`ALKERMES PHARMA IRELAND LIMITED
`Patent Owner
`__________________
`
`Case No. IPR2025-00514
`Patent 7,919,499
`__________________
`
`DECLARATION OF THOMAS CHARLES DOWLING, Pharm.D., Ph.D. IN
`SUPPORT OF PETITION FOR INTER PARTES REVIEW OF U.S.
`PATENT NO. 7,919,499
`
`APOTEX EXHIBIT 1046
`Apotex v. Alkermes
`IPR2025-00514
`
`

`

`
`Page
`INTRODUCTION ........................................................................................... 1
`BACKGROUND AND QUALIFICATIONS ................................................. 2
`INFORMATION CONSIDERED ................................................................... 7
`
` RELEVANT LEGAL STANDARDS ............................................................. 7
`Claim Interpretation .............................................................................. 7
`Perspective of One of Ordinary Skill in the Art .................................... 7
`Anticipation ........................................................................................... 8
`
` Obviousness ........................................................................................... 8
`SUMMARY OF OPINIONs ......................................................................... 11
` THE CHALLENGED ’499 Patent ................................................................ 11
` LEVEL OF ORDINARY SKILL IN THE ART ........................................... 11
` TECHNICAL BACKGROUND ................................................................... 13
`The Purported Invention ...................................................................... 13
`Pertinent Prosecution History Of The ’499 Patent .............................. 18
`Summary of the Applied Prior Art ...................................................... 20
`1.
`Comer (EX1004) ....................................................................... 20
`2.
`Nuwayser (EX1005) ................................................................. 23
`3.
`Rubio (EX1006) ........................................................................ 24
`4. Wright (EX1007) ...................................................................... 25
`5.
`Kranzler (EX1008) .................................................................... 25
`State Of The Art .................................................................................. 26
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`TABLE OF CONTENTS
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`i
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`
`
`
`
`The Area Under the Curve (AUC) ...................................................... 28
`AUC Does Not Meaningfully Impact Efficacy ................................... 31
`
` A POSITA Would Find the Claimed Comparison Inapt .................... 33
`The Claimed AUC Differential is Known or Would be
`Apparent .............................................................................................. 36
`1.
`The AUC of Comer ................................................................... 36
`2.
`The AUC of Nuwayser ............................................................. 43
` CLAIM CONSTRUCTION .......................................................................... 45
`“the step of parenterally administering a long acting
`formulation comprising about 310 mg to about 480 mg of
`naltrexone” .......................................................................................... 45
`“the serum AUC of naltrexone … than that achieved by 50
`mg/day oral administration” ................................................................ 46
`“about three” ........................................................................................ 48
`“five or more days” ............................................................................. 49
`“initial oral dose” ................................................................................. 50
`“about 35% by weight” ....................................................................... 51
`
`THE CHALLENGED CLAIMS ARE ANTICIPATED OR OBVIOUS IN
`VIEW OF THE PRIOR ART ........................................................................ 51
` Ground 1: Claims 1, 3-5, and 12 Are Anticipated by Comer ............. 51
`1.
`Claim 1 (Preamble): A method for treating an individual
`in need of naltrexone comprising the step of ............................ 52
`a.
`[1.1]: parenterally administering a long acting
`formulation comprising .................................................. 52
`[1.2]: about 310 mg to about 480 mg of naltrexone ....... 54
`
`b.
`
`
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`ii
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`c.
`
`d.
`
`e.
`
`2.
`
`4.
`
`5.
`
`3.
`
`[1.3]: and a biocompatible polymer to the
`individual ........................................................................ 55
`[1.4]: wherein the serum AUC of naltrexone is
`about three times greater than that achieved by 50
`mg/day oral administration ............................................. 55
`[1.5]: and wherein the biocompatible polymer is a
`polylactide-co-glycolide polymer. .................................. 57
`Claim 3: The method of claim 1 wherein the long acting
`formulation releases naltrexone for a period of at least
`two weeks. ................................................................................. 57
`Claim 4: The method of claim 1 wherein the long acting
`formulation releases naltrexone for a period of about four
`weeks. ........................................................................................ 58
`Claim 5: The method of claim 1 wherein the long acting
`formulation is administered in a dose of about 380 mg of
`naltrexone wherein the serum AUC is about 3.3 times
`greater than that achieved by 50 mg/day oral
`administration. ........................................................................... 58
`Claim 12: The method of claim 1 wherein naltrexone is
`administered by injection. ......................................................... 59
`Ground 2: Claims 1-13 Would Have Been Obvious Over
`Comer in view of Nuwayser, Rubio, and Wright ............................... 59
`1.
`Claim 1 ...................................................................................... 62
`2.
`Claim 2 ...................................................................................... 66
`3.
`Claim 3 ...................................................................................... 66
`4.
`Claim 4 ...................................................................................... 67
`5.
`Claim 5 ...................................................................................... 67
`6.
`Claim 6 ...................................................................................... 67
`7.
`Claims 7-9 ................................................................................. 68
`
`iii
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`

`

`
`
`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`b.
`c.
`
`d.
`
`8.
`Claim 10 .................................................................................... 69
`Claim 11 .................................................................................... 69
`9.
`10. Claim 12 .................................................................................... 70
`11. Claim 13 .................................................................................... 70
`Ground 3: Claims 1-13 Would Have Been Obvious Over
`Nuwayser in View of Comer, Rubio, and Wright ............................... 71
`1.
`Claim 1 (Preamble): A method for treating an individual
`in need of naltrexone comprising the step of ............................ 71
`a.
`[1.1]: parenterally administering a long acting
`formulation comprising .................................................. 74
`[1.2]: about 310 mg to about 480 mg of naltrexone ....... 74
`[1.3]: and a biocompatible polymer to the
`individual ........................................................................ 77
`[1.4]: wherein the serum AUC of naltrexone is
`about three times greater than that achieved by 50
`mg/day oral administration ............................................. 77
`[1.5]: and wherein the biocompatible polymer is a
`polylactide-co-glycolide polymer. .................................. 78
`Claim 2 ...................................................................................... 78
`Claim 3 ...................................................................................... 79
`Claim 4 ...................................................................................... 79
`Claim 5 ...................................................................................... 79
`Claim 6 ...................................................................................... 79
`Claims 7-9 ................................................................................. 80
`Claim 10 .................................................................................... 80
`Claim 11 .................................................................................... 80
`
`2.
`3.
`4.
`5.
`6.
`7.
`8.
`9.
`
`e.
`
`iv
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`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`10. Claim 12 .................................................................................... 80
`11. Claim 13 .................................................................................... 80
` Ground 4: Claims 1-13 Would Have Been Obvious Over
`Nuwayser in view of Kranzler, Rubio, and Wright . Error! Bookmark
`not defined.
` OTHER CONSIDERATIONS ...................................................................... 81
` Any Purported Secondary Considerations Evidence Does Not
`Overcome the Strong Evidence of the Obviousness of the
`Claims .................................................................................................. 81
` CONCLUSION ................................................................................................ 1
`
`
`
`
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`
`v
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`
`
`EXHIBIT LIST
`
`EXHIBIT DESCRIPTION
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`U.S. Patent No. 7,919,499, issued on April 5, 2011 to E. Ehrich
`(“the ’499 Patent”)
`
`File History of U.S. Patent Application No. 11/083,167, filed on
`March 17, 2005 (“the ’167 Application)
`
`U.S. Provisional Application No. 60/564,542, filed on April 22,
`2004
`
`Sandra D. Comer et al., Depot naltrexone: long-lasting
`antagonism of the effects of heroin in humans, 159(4)
`Psychopharmacology (Feb. 2002), at 351-360
`
`U.S. Patent No. 7,157,102, issued on January 2, 2007 to E.
`Nuwayser (“the ’102 Patent” or “Nuwayser”)
`
`G. Rubio et al., Naltrexone Versus Acamprosate: One Year
`Follow-Up of Alcohol Dependence Treatment, 36(5) Alcohol &
`Alcoholism (2001), at 419-425
`
`U.S. Patent No. 6,264,987, issued on July 24, 2001 to S. Wright
`et al. (“the ’987 Patent” or “Wright”)
`
`Henry R. Kranzler et al., Sustained-Release Naltrexone for
`Alcoholism Treatment: A Preliminary Study, 22(5) Alcoholism:
`Clinical and Experimental Research (Aug. 1998), at 1074-79
`
`U.S. Patent No. 6,306,425, issued on October 23, 2001 to T.
`Tice et al. (“Tice”)
`
`C.N. Chiang et al., Clinical Evaluation of A Naltrexone
`Sustained-Release Preparation, 16 Drug & Alcohol Dependence
`(1985), at 1-8
`
`vi
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`EXHIBIT DESCRIPTION
`
`1011
`
`1012
`
`1013
`
`1014
`
`1016
`
`1017
`
`1018
`
`1019
`
`T.N. Alim et al., Tolerability Study of A Depot Form of
`Naltrexone Substance Abusers, Problems of Drug Dependence,
`1994: Proceedings of the 56th Annual Scientific Meeting, The
`College on Problems of Drug Dependence, Inc., Vol. II:
`Abstracts, National Institute on Drug Abuse Research
`Monograph 153 (1995), at 253
`
`U.S. Securities and Exchange Commission, FORM 10-K, Annual
`Report Pursuant to Section 13 or 15(d) of the Securities
`Exchange Act of 1934 for the fiscal year ended March 31, 2002.
`Alkermes, Inc. (July 2002)
`
`U.S. Trademark Application Serial Number 76/271,990,
`Allegation of Use of a Mark & specimen of the mark as used in
`commerce, Aug. 15, 2002 (“Vivitrex Specimen” or “Specimen”)
`
`S.J. Heishman et al., Safety And Pharmacokinetics of a New
`Formulation of Depot Naltrexone, Problems of Drug
`Dependence, 1993: Proceedings of the 55th Annual Scientific
`Meeting, The College on Problems of Drug Dependence, Inc.,
`Volume II: Abstracts, National Institute on Drug Abuse
`Research Monograph 141 (1994)
`
`Stewart B. Leavitt, PhD, ed., Evidence for the Efficacy of
`Naltrexone in the Treatment of Alcohol Dependence
`(Alcoholism), Addition Treatment Forum Naltrexone Clinical
`Update (2002 Clinco Communications, Inc.), at 1-8
`
`ReVia, Physicians’ Desk Reference 936-938 (53rd ed. 1999)
`(“PDR”)
`
`U.S. Patent No. 4,882,335, issued on November 21, 1989 to J.
`Sinclair (“Sinclair”)
`
`Chiang et al., Kinetics of a naltrexone sustained-release
`preparation, 36(5) Clin. Pharmacol. Ther. (Nov. 1984), at 704-
`08 “Kinetic of a naltrexone sustained-release preparation.”
`
`vii
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`EXHIBIT DESCRIPTION
`
`1020
`
`1021
`
`1025
`
`1029
`
`1033
`
`1034
`
`1035
`
`1037
`
`1038
`
`1039
`
`Reuning et al., Pharmacokinetic Quantitation of Naltrexone
`Release From Several Sustained-Release Delivery Systems,
`Naltrexone: Research Monograph 28 (R. E. Willette and G.
`Barnett, eds. National Institute on Drug Abuse 1980)
`
`Appeal Brief, Application No. 13/871,534, Oct. 19, 2015
`
`Orange Book: Approved Drug Products with Therapeutic
`Equivalence Evaluations, Product Details for NDA 018932,
`REVIA (NALTREXONE HYDROCHLORIDE) 50MG
`
`TREXAN™, Physicians’ Desk Reference 936-938 (46 ed. 1992)
`(“PDR”), at 937-939
`
`Bertil Abrahamsson and Anna-Lena Ungell, Biopharmaceutical
`support in formulation development:A Practical Guide from
`Candidate Drug Selection to Commercial Dosage Form,
`Pharmaceutical Preformulation and Formulation (Mark Gibson
`ed., Interpharm/CRC) (2004), 239-291, at 262
`
`Guidance for Industry. Bioavailability and Bioequivalence
`Studies for Orally Administered Products—General
`Considerations. FDA CDER (March 2003)
`
`Riddle et al., Anxiolytics, adrenergic agents, and naltrexone,
`38(5) J. Am. Acad. Child. Adolesc. Psychiatry, 546-556 (May
`1999)
`
`Rothenberg et al., Behavioral naltrexone therapy: an integrated
`treatment for opiate dependence, 23 J. of Substance Abuse
`Treatment (2002), at 351-360
`
`B.A. Johnson, Naltrexone long-acting formulation in the
`treatment of alcohol dependence, 3(5) Ther. Clin. Risk Manag.,
`741-749 (2007), at 742.
`
`Food and Drug Administration, Guidance for Industry,
`Exposure-response relationships – study design, data analysis,
`and regulatory applications, FDA CDER (April 2003)
`
`viii
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`EXHIBIT DESCRIPTION
`
`1040
`
`1041
`
`1042
`
`1047
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058
`
`1060
`
`1061
`
`1062
`
`Food and Drug Administration, Guidance for Industry,
`Statistical approaches to establishing bioequivalence, FDA
`CDER (April 2003)
`
`Schenker et al., Antecedent liver disease and drug toxicity, 31 J.
`of Hepatology 1098-1105 (1999)
`
`U.S. Patent No. 3,332,950, issued on July 25, 1997 to H.
`Blumberg
`
`Curriculum Vitae of Thomas Dowling
`
`Resume of Mike Ramstack, as obtained from LinkedIn
`
`Resume of Richard Reuning, as obtained from LinkedIn
`
`Resume of Steve Wright, as obtained from LinkedIn
`
`Declaration Under 37 C.F.R. §1.132 of Elliot Ehrich filed in
`Application No. Serial No. 11/083,167
`
`S. Hamilton et al., Pharmacokinetics and Pharmacodynamics of
`Hyaluronan Infused Healthy Human Volunteers, 3 The Open
`Drug Metabolism Journal 43-55 (2009)
`
`Trademark Registration No. 2,443,435 (Depotrex)
`
`Institution Decision entered November 7, 2018 (Paper 8) in
`IPR2018-00943
`
`Patent Owner’s Response, filed February 7, 2019 (Paper 14) in
`IPR2018-00943
`
`U.S. Patent No. 5,210,083, issued on May 11, 1993 to R.
`Pfirrmann
`
`U.S. Patent No. 5,234,906, issued on August 10, 1993 to A.
`Young and G. Cooper
`
`ix
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`EXHIBIT DESCRIPTION
`
`1063
`
`1064
`
`1065
`
`1066
`
`U.S. Patent No. 6,677,320, issued on January 13, 2004 to A.
`Diederich et al.
`
`U.S. Patent No. 6,120,787, issued on September 19, 2000 to
`N.O. Gustafsson et al.
`
`U.S. Patent Publication No. 2003/0211167, published on
`November 13, 2003
`
`U.S. Patent No. 6,455,526, issued on September 24, 2002 to R.
`Kohn et al.
`
`
`
`
`x
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`I, Thomas Charles Dowling, Pharm. D., Ph.D., declare and state as follows
`
`
`
`INTRODUCTION
`1.
`I am a U.S. citizen and a resident of the State of Michigan.
`
`2.
`
`I have been retained by Buchanan Ingersoll & Rooney PC (“Counsel”)
`
`to provide my opinions in the field of pharmaceutical formulation for purposes of
`
`supporting a petition for Inter Partes Review (“IPR”). I have read and understand
`
`U.S. Patent No. 7,919,499 (“the ’499 Patent”) (EX1001) as well as all other
`
`references discussed in this declaration. I am being compensated for my time in an
`
`amount consistent with my customary consulting fee, and my compensation is not
`
`contingent on my opinion or the outcome of this proceeding.
`
`3.
`
`I have been asked by Counsel to provide opinions regarding Claims
`
`1-13 of United States Patent No. 7,919,499 (“the ’499 Patent”). My opinions and the
`
`bases for my opinions are set forth below.
`
`4.
`
`This report is based on information currently available to me. I reserve
`
`the right to continue my investigation and analysis, which may include a review of
`
`documents and information not listed above. I also reserve the right to expand or
`
`otherwise modify my opinions and conclusions as my investigation and study
`
`continues, and to supplement my opinions and conclusions in response to any
`
`additional information that becomes available to me.
`
`1
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`
`
`BACKGROUND AND QUALIFICATIONS
`5.
`I am a clinical pharmacologist with over 20 years of experience in
`
`research and teaching in the areas of biopharmaceutics, advanced pharmacokinetics,
`
`and clinical pharmacokinetics. I received a Pharm.D. from Ferris State University
`
`(with high distinction) followed by a residency in pharmacy practice at the
`
`University of Maryland Medical System.
`
`6.
`
`During my residency, I conducted research on drug pharmacokinetics,
`
`along with antibiotic surveillance in collaboration with the Centers for Disease
`
`Control, leading to a seminal publication in the Annals of Internal Medicine. This
`
`publication has been cited nearly 600 times since 1995.
`
`7.
`
`I subsequently received a Ph.D. in Pharmaceutical Sciences from the
`
`University of Pittsburgh, where my research work focused upon clinical
`
`pharmacokinetics and pharmacokinetic modeling of drug elimination. Three of my
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`dissertation chapters were published in leading scientific journals including
`
`Pharmacotherapy, Journal of Chromatography B Biomedical Applications, and
`
`Kidney International.
`
`8.
`
`I was appointed as an Assistant Professor of Pharmacy in 1999 at the
`
`University of Maryland School of Pharmacy, and developed a successful research
`
`program in clinical pharmacokinetics, biopharmaceutics, and drug elimination
`
`metabolism. My research projects have been funded by organizations such as the
`
`2
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`American College of Clinical Pharmacy and American Foundation for
`
`Pharmaceutical Education, with federal funding from agencies such as the National
`
`Institutes of Health (NIH) and the U.S. Food and Drug Administration (FDA).
`
`9.
`
`I was the first researcher in the School of Pharmacy to conduct a clinical
`
`trial at the University of Maryland General Clinical Research Center and have
`
`subsequently served as a principal or co-principal investigator on at least 15 clinical
`
`pharmacokinetics studies evaluating blood levels of drugs or biomarkers in the body
`
`since 2000.
`
`10.
`
`I was an original member of the University of Maryland Clinical
`
`Research Working Group and the Program in Genetics and Genomic Medicine and
`
`served as a mentor for the University of Maryland NIH K30 Clinical Research
`
`Training Program.
`
`11.
`
`I was appointed by the Dean of the University of Maryland School of
`
`Medicine to a 3-year term as a voting member of the University of Maryland
`
`Institutional Review Board (IRB).
`
`12.
`
`I am, or have been, a member and have held national leadership
`
`positions in many scientific and professional societies. In the American College of
`
`Clinical Pharmacy, I served as Chairman of the Research Affairs Committee and
`
`was elected to the ACCP Research Institute Board of Trustees. I am an editorial
`
`board member for the journal Pharmacotherapy and serve as a manuscript referee
`
`3
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`for many leading pharmacokinetics journals such as Clinical Pharmacokinetics,
`
`Biopharmaceutics and Drug Disposition and Pharmaceutical Research. I have served
`
`as a consultant and voting member as a pharmacokinetics expert on multiple FDA
`
`advisory committees (and topics) including the FDA Advisory Committee for
`
`Pharmaceutical Science and Clinical Pharmacology (pharmacogenomics, drug
`
`safety, pharmacokinetics, drug metabolism, transport-mediated drug interactions),
`
`the FDA Advisory Committee on Anti-Infective Drugs (PK/PD of antimicrobial
`
`agents) and FDA Advisory Committee on Pulmonary-Allergy Drugs
`
`(pharmacokinetics review of NDA 214697).
`
`13.
`
`In 2004, I received the Teacher of the Year award at the University of
`
`Maryland School of Pharmacy, which was voted upon by my faculty peers. I have
`
`served as primary dissertation advisor to four Ph.D. students, who have subsequently
`
`pursued careers in the pharmaceutical industry (Abbott Laboratories, Bristol Myers
`
`Squibb), clinical research (University of Maryland, Division of Transplantation),
`
`and the FDA (Office of Clinical Pharmacology, Genomics group). In 2005, I was
`
`promoted to Associate Professor (with tenure) and was promoted to full Professor
`
`with tenure in 2014. I am currently Assistant Dean in the College of Pharmacy at
`
`Ferris State University, focusing on research and development. I also serve as the
`
`Director of the Office of Research and Sponsored Programs at Ferris State
`
`University.
`
`4
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`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`14. To date, I have published over 100 works that have been cited nearly
`
`3,000 times with an H-index of 29.1 I have published manuscripts and have written
`
`chapters in leading clinical pharmacology and pharmacokinetics textbooks such as
`
`DiPiro’s Pharmacotherapy, Winter’s Basic Clinical Pharmacokinetics, and
`
`Murphy’s Clinical Pharmacokinetics. I have designed and conducted many clinical
`
`trials involving the analysis of pharmacokinetic parameters and other clinical data. I
`
`have expertise in developing and validating bioanalytical assays to support
`
`pharmacokinetic studies.
`
`15.
`
`I have expertise in evaluating biopharmaceutics and drug absorption,
`
`including transdermal absorption of ketoprofen gel and excipient-related effects on
`
`the Cmax and AUC of single-dose formulations of cimetidine, ciprofloxacin, and
`
`acyclovir using 4-way crossover studies in healthy volunteers. I have served as the
`
`principal investigator on industry-sponsored and FDA-regulated trials evaluating
`
`bioequivalence of generic drugs and other compounds. I have served as a principal
`
`investigator on studies evaluating formulation effects on bioequivalence and other
`
`studies that were funded by the FDA’s Critical Path Initiative. Along with co-
`
`investigators from the FDA, the results of these studies were published in high
`
`
`
`1 See Google Scholar:
`
`https://scholar.google.com/citations?user=L0aHm1UAAAAJ&hl=en&oi=ao.
`
`5
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`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`impact journals including the Journal of Pharmaceutical Sciences (2016), AAPS
`
`Journal (2016), and Regulatory Toxicology and Pharmacology (2013).
`
`16.
`
`I have received nearly $3 million in extramural funding as an
`
`investigator or project director from agencies including the NIH, FDA, and the
`
`National Institutes of Standards and Technology (NIST). My research work has been
`
`presented at major national and international scientific symposia such as the
`
`American College of Clinical Pharmacology, the American Society for Clinical
`
`Pharmacology and Therapeutics, the FDA’s Office of Clinical Pharmacology Grand
`
`Rounds and the FDA’s Science Day Symposium.
`
`17.
`
`In 2009, I was elected a Fellow of the American College of Clinical
`
`Pharmacology (FCP) and in 2010 was elected a Fellow of the American College of
`
`Clinical Pharmacy (FCCP).
`
`18. My CV, which includes a list of all my publications, is attached as
`
`EX1047. In summary, I am an expert in the areas described herein and I qualify as
`
`at least a person of ordinary skill in the art (“POSITA” or a “person of ordinary skill
`
`in the art”) under the definitions previously set forth by the parties in IPR2018-
`
`00943.
`
`6
`
`

`

`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
`
`
`
`INFORMATION CONSIDERED
`19.
`In preparing this declaration, I have reviewed the ’499 Patent and the
`
`exhibits and documents referenced herein. In addition, my opinions are further
`
`based on my education, training, experience, and knowledge in the relevant field.
`
` RELEVANT LEGAL STANDARDS
`20.
`I am not an attorney and offer no legal opinions. For the purposes of
`
`this Declaration, I have been informed about certain aspects of the law that are
`
`relevant to my analysis, as summarized below.
`
` Claim Interpretation
`21.
`I have been informed that during an inter partes review proceeding,
`
`claims are to be construed in light of the specification as would be read by a person
`
`of ordinary skill in the relevant art at the time the application was filed. I have been
`
`informed that claim terms are given their ordinary and customary meaning as would
`
`be understood by a person of ordinary skill in the relevant art in the context of the
`
`entire disclosure. A claim term, however, will not receive its ordinary meaning if the
`
`patentee acted as his own lexicographer and clearly set forth a definition of the claim
`
`term in the specification. In that case, the claim term will receive the definition set
`
`forth in the patent.
`
`
`22.
`
`Perspective of One of Ordinary Skill in the Art
`I have been informed that a patent is to be understood from the
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`perspective of a hypothetical “person of ordinary skill in the art” (“POSITA”). Such
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
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`an individual is considered to possess normal skills and knowledge in a particular
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`technical field (as opposed to being a genius). I have been informed that in
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`considering what the claims of a patent require, what was known prior to that patent,
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`what a prior art reference discloses, and whether an invention is obvious or not, one
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`must use the perspective of such a POSITA.
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` Anticipation
`23.
`I have been informed that a claim is not patentable if it is anticipated. I
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`have been informed that anticipation of a claim requires that every element of a claim
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`is disclosed expressly or inherently in a prior art reference, arranged as in the claim,
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`when considered from the perspective of a person of ordinary skill in the relevant
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`art. I have been informed that when the structure recited in a reference is
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`substantially identical to that of the claims, claimed properties or functions are
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`presumed to be inherent. I have been informed that extrinsic evidence may be used
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`to explain but not expand the meaning of terms and phrases used in the reference
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`relied upon as anticipatory of the claimed subject matter.
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` Obviousness
`24.
`I have been informed that a patent claim is obvious under 35 U.S.C. §
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`103, and therefore invalid, if the claimed subject matter, as a whole, would have
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`been obvious to a POSITA as of the priority date of the patent based on one or more
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`prior art references and/or the knowledge of a POSITA.
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
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`25.
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`I have been informed that an obviousness analysis must consider (1) the
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`scope and content of the prior art, (2) the differences between the claims and the
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`prior art, (3) the level of ordinary skill in the pertinent art, and (4) secondary
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`considerations, if any, of non-obviousness (such as unexpected results, commercial
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`success, long- felt but unmet need, failure of others, copying by others, and
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`skepticism of experts).
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`26.
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`I have been informed that a prior art reference may be combined with
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`other references to disclose each element of the invention under 35 U.S.C. § 103. I
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`have been informed that a reference may also be combined with the knowledge of a
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`POSITA, and that this knowledge may be used to combine multiple references. I
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`have been informed that a POSITA is presumed to know the relevant prior art. I have
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`been informed that the obviousness analysis may take into account the inferences
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`and creative steps that a POSITA would employ.
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`27.
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`In determining whether a prior art reference would have been combined
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`with other prior art or other information known to a POSITA, I have been informed
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`that the following principles may be considered:
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`•
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`•
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`whether the references to be combined involve non-analogous art;
`whether the references to be combined are in different fields of
`endeavor than the alleged invention in the patent;
`whether the references to be combined are reasonably pertinent to the
`problems to which the inventions of the patent are directed;
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
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`whether the combination is of familiar elements according to known
`methods that yields predictable results;
`whether a combination involves the substitution of one known
`element for another that yields predictable results;
`whether the combination involves the use of a known technique to
`improve similar items or methods in the same way that yields
`predictable results;
`whether the combination involves the application of a known
`technique to a prior art reference that is ready for improvement, to
`yield predictable results;
`whether the combination is “obvious to try”;
`whether the combination involves the 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,
`where the variations are predictable to a POSITA;
`whether there is some teaching, suggestion, or motivation in the prior
`art that would have led one of ordinary skill in the art to modify the
`prior art reference or to combine prior art reference teachings to arrive
`at the claimed invention;
`whether the combination requires modifications that render the prior
`art unsatisfactory for its intended use;
`whether the combination requires modifications that change the
`principle of operation of the reference;
`whether the combination is reasonably expected to be a success; and
`whether the combination possesses the requisite degree of
`predictability at the time the invention was made.
`I have been informed that in determining whether a combination of
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`•
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`28.
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`prior art references renders a claim obvious, it is helpful to consider whether there is
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`some teaching, suggestion, or motivation to combine the references and a reasonable
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`Declaration of Thomas Charles Dowling, Pharm.D., Ph.D.
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`expectation of success in doing so. I have been informed, however, that a teaching,
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`suggestion, or motivation to combineis not required.
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`V.
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`SUMMARYOF OPINIONS
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`29.
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`It is my opinion that Claims 1-13 of the ’499 Patent would have been
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`anticipated or obvious on the following grounds:
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`!
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`$102(6)
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`1, 3-5, 12
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`Comer (EX1004) as evidenced by
`Nuwayser (EX1005)
`Comer in view of Nuwayser,
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`(EX1007)
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`2|Rubio (EX1006), and Wright 1-13
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`VI.
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`THE CHALLENGED ’499 PATENT
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`30.
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`The ’499 Patent contains 15 claims. I have been asked to opine on the
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`validity of Claims 1-13.
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`Vil. LEVEL OF ORDINARYSKILL IN THE ART
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`31.
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`I have been informed that a POSITA is presumedto be awareofall
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`pertinent art, thinks along conventional wisdom in the art, and is a person of
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`ordinary creativity.
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`32.
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`For the purposesofthis proceeding,I agree with the POSITAdef