`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`MYLAN PHARMACEUTICALS INC., DR. REDDY’S LABORATORIES, INC.,
`and DR. REDDY’S LABORATORIES, LTD.,
`Petitioner,
`v.
`NOVO NORDISK A/S,
`Patent Owner.
`
`IPR2023-007241
`Patent 10,335,462 B2
`
`Reply Declaration of Dr. Allen Spiegel
`
`
`
`
`
`
`
`
`
`
`1 IPR2024-00009 (Dr. Reddy’s Laboratories) has been joined with this proceeding.
`
`
`
`MPI EXHIBIT 1302 PAGE 1
`
`

`

`TABLE OF CONTENTS
`
`
`
`I.
`
`Qualifications and Background .....................................................................11
`A.
`Education and Experience; Prior Testimony.......................................11
`B.
`Basis of Opinions and Materials Considered ......................................14
`C.
`Retention and Compensation ..............................................................15
`Summary of Opinions ....................................................................................15
`II.
`III. Legal Standards .............................................................................................16
`IV. Person of Ordinary Skill in the Art ................................................................22
`V.
`Relevant Novo Nordisk Patents and Claims .................................................24
`A.
`Challenged Patent - U.S. Patent No. 10,335,462 ................................25
`B.
`U.S. Patent No. 8,129,343 ...................................................................29
`C.
`U.S. Patent No. 8,536,122 ...................................................................33
`D. U.S. Patent No. 8,114,833 ...................................................................36
`VI. Claim Constructions ......................................................................................38
`VII. Technical Background and Prior Art .............................................................39
`A. Diabetes, generally ..............................................................................39
`B.
`Diabetes treatments .............................................................................42
`C.
`GLP-1 receptor agonists and class-wide treatment effects .................47
`1. Early GLP-1 receptor agonists ............................................49
`2. GLP-1 receptor agonists as a class were understood to
`reduce HbA1c and body weight ................................................50
`3. Liraglutide (Victoza® and Saxenda®) ...............................52
`4. Semaglutide (Ozempic®) ...................................................56
`Patent Owner’s related patent and approved product to reduce body
`D.
`weight.............................................................................................................60
`1. U.S. Patent No. 9,764,003 ..................................................60
`2. Wegovy® ............................................................................63
`The SUSTAIN Trials ..........................................................................65
`E.
`VIII. Secondary Considerations Opinions ..............................................................69
`
`2
`
`MPI EXHIBIT 1302 PAGE 2
`
`

`

`TABLE OF CONTENTS
`A. General deficiencies in the Goland Declaration’s opinions ................69
`1. The Goland Declaration failed to compare the ’462 patent’s
`claimed semaglutide once weekly 1.0 mg dosing regimen to the
`closest prior art ..........................................................................70
`2. The Goland Declaration failed to support much of its
`reasoning ...................................................................................72
`3. The Goland Declaration erroneously suggested that the use
`of Ozempic® according to its label has a nexus with the ’462
`patent’s claimed semaglutide once weekly 1.0 mg dosing
`regimen ......................................................................................74
`The Goland Declaration did not establish any secondary
`B.
`considerations to support a finding of nonobviousness .................................81
`1. The Goland Declaration failed to establish with relevant
`evidence that the inventions claimed in the ’462 patent yielded
`unexpected results .....................................................................81
`2. The Goland Declaration failed to establish with relevant
`evidence that the inventions claimed in the ’462 patent satisfied
`a long-felt but unmet need in the art .........................................98
`3. The Goland Declaration failed to establish with relevant
`evidence that the inventions claimed in the ’462 patent have
`been the subject of praise ........................................................103
`4. The Goland Declaration failed to establish with relevant
`evidence that there was skepticism toward the inventions
`claimed in the ’462 patent .......................................................110
`IX. Reservation of Rights ..................................................................................114
`
`
`
`
`
`
`3
`
`MPI EXHIBIT 1302 PAGE 3
`
`

`

`TABLE OF ABBREVIATIONS
`
`
`Full Name of Cited Reference
`U.S. Patent No. 9,764,003
`
`U.S. Patent No. 8,536,122
`
`U.S. Patent No. 8,129,343
`
`U.S. Patent No. 10,335,462
`
`U.S. Patent No. 8,114,833
`
`American Diabetes Association, Pharmacologic
`Approaches to Glycemic Treatment: Standards of Care in
`Diabetes-2023, 46 DIABETES CARE S140 (2023)
`Astrup et al., Effects of Liraglutide in the Treatment of
`Obesity: A Randomised, Double-Blind, Placebo-
`Controlled Study, 374 LANCET 1606 (2009)
`Bhansali et al., Historical Overview of Incretin Based
`Therapies, 58 SUPPL. TO JAPI 10 (2010)
`Buse et al., Liraglutide Once a Day Versus Exenatide
`Twice a Day for Type 2 Diabetes: A 26-Week
`Randomised, Parallel-Group, Multinational, Open-Label
`Trial (LEAD-6), 374 LANCET 39 (2009)
`Highlights of Prescribing Information: Byetta,
`Rev. 1/2012
`Highlights of Prescribing Information: Byetta,
`Rev. 10/2009
`Centers for Disease Control and Prevention National
`Diabetes Statistics Report
`https://www.cdc.gov/diabetes/data/statistics-
`report/index.html (last accessed May 1, 2024)
`
`Abbreviation
`’003 patent
`(EX2002)
`’122 patent
`(EX1067)
`’343 patent
`(EX1068)
`’462 patent
`(EX1001)
`’833 patent
`(EX1121)
`ADA Standards 2023
`(EX1122)
`
`Astrup
`(EX1096)
`
`Bhansali
`(EX1137)
`Buse
`(EX1114)
`
`Bydureon label
`(EX1020)
`Byetta label
`(EX1021)
`CDC Report
`(EX1115)
`
`4
`
`MPI EXHIBIT 1302 PAGE 4
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`CECIL TEXTBOOK OF MEDICINE, Chapters 233 (Obesity)
`and 242 (Diabetes Mellitus) (Goldman et al. eds., 22nd
`ed. 2004)
`Applah, My Best Friends Are Taking Ozempic. Can I
`Share My Disapproval?, New York Times (June 28,
`2023)
`Drab, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus: Current Status and Future Prospects, 30
`PHARMACOTHERAPY 609 (2010)
`Garber et al., Liraglutide Versus Glimepiride
`Monotherapy for Type 2 Diabetes (LEAD-3 Mono): A
`Randomised, 52-Week, Phase III, Double-Blind, Parallel-
`Treatment Trial, 373 LANCET 473 (2009)
`Garber et al., Liraglutide, A Once-Daily Human
`Glucagon-Like Peptide 1 Analogue, Provides Sustained
`Improvements in Glycaemic Control and Weight for 2
`Years as Monotherapy Compared with Glimepiride in
`Patients with Type 2 Diabetes, 13 DIABETES OBESITY &
`METABOLISM 348 (2011)
`Garber, Long-Acting Glucagon-Like Peptide 1 Receptor
`Agonists, 34 DIABETES CARE S279 (2011)
`Transcript of the April 9, 2024 Deposition of Robin S.
`Goland, M.D.
`GRADE Research Study Group, Glycemia Reduction in
`Type 2 Diabetes — Glycemic Outcomes, 387 NEW ENG. J.
`MED. 1063 (2022)
`Grunberger et al., Monotherapy with the Once-Weekly
`GLP-1 Analogue Dulaglutide for 12 Weeks in Patients
`with Type 2 Diabetes: Dose-Dependent Effects on
`Glycaemic Control in a Randomized, Double-Blind,
`Placebo-Controlled Study, 29 DIABETIC MEDICINE 1260
`(2012)
`
`Abbreviation
`Cecil
`(EX1129)
`
`Disapproval
`(EX1117)
`
`Drab
`(EX1022)
`
`Garber 2009
`(EX1097)
`
`Garber 2011a
`(EX1098)
`
`Garber 2011b
`(EX1099)
`Goland Dep.
`(EX1140)
`GRADE
`(EX1124)
`
`Grunberger
`(EX1109)
`
`
`
`5
`
`MPI EXHIBIT 1302 PAGE 5
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`HARRISON’S PRINCIPLES OF INTERNAL MEDICINE, Chapters
`74 (Biology of Obesity), 75 (Evaluation and Management
`of Obesity), and 338 (Diabetes Mellitus) (Fauci et al. eds.,
`17th ed. 2008)
`Holst, Glucagon-Like Peptide 1 and Inhibitors of
`Dipeptidyl Peptidase IV in the Treatment of Type 2
`Diabetes Mellitus, CURRENT OPINION IN PHARMACOLOGY
`589 (2004)
`Holst, The Incretin Approach for Diabetes Treatment, 53
`DIABETES S197 (2004)
`Jimenez-Solem et al., Dulaglutide, a Long-Acting GLP-1
`Analog Fused with an Fc Antibody Fragment for the
`Potential Treatment of Type 2 Diabetes, 12 CURRENT
`OPINION IN MOLECULAR THERAPEUTICS 790 (2010)
`Jose et al., Exenatide Once Weekly: Clinical Outcomes
`and Patient Satisfaction, 4 PATIENT PREFERENCE &
`ADHERENCE 313 (2010)
`Karagiannis et al., Subcutaneously Administered
`Tirzepatide vs Semaglutide for Adults with Type 2
`Diabetes: A Systematic Review and Network
`Meta‑Analysis of Randomised Controlled Trials,
`DIABETOLOGIA (published online Apr. 13, 2024)
`Knudsen, Liraglutide, a GLP-1 Analogue to Treat
`Diabetes in ANALOGUE-BASED DRUG DISCOVERY II
`(Fischer and Ganellin eds. 2010)
`U.S. Patent No. 6,268,343
`
`Lorenz et al., Recent Progress and Future Options in the
`Development of GLP-1 Receptor Agonists for the
`Treatment of Diabesity, 23 BIOORGANIC & MED. CHEM.
`LETTERS 4011 (2013)
`Lovshin, Incretin-based Therapies for Type 2 Diabetes
`Mellitus, 5 NATURE REVIEWS ENDOCRINOLOGY 262
`(2009)
`
`Abbreviation
`Harrison’s
`(EX1136)
`
`Holst 2004a
`(EX1028)
`
`Holst 2004b
`(EX1138)
`Jimenez-Solem
`(EX1029)
`
`Jose
`(EX1100)
`
`Karagiannis
`(EX1110)
`
`Knudsen
`(EX1033)
`
`Knudsen patent
`(EX1034)
`Lorenz
`(EX1139)
`
`Lovshin
`(EX1012)
`
`
`
`6
`
`MPI EXHIBIT 1302 PAGE 6
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`Lund, Emerging GLP-1 Receptor Agonists, 16 EXPERT
`OPINION ON EMERGING DRUGS 607 (2011)
`Madsbad, Review of Head-to-Head Comparisons of
`Glucagon-Like Peptide-1 Receptor Agonists, 18 DIABETES
`OBESITY & METABOLISM 317 (2016)
`Highlights of Prescribing Information: Mounjaro,
`Rev. 5/2022
`Clinicaltrials.gov identifier: NCT00422058 (The Effect of
`Liraglutide on Body Weight in Obese Subjects Without
`Diabetes) Feb. 19, 2011 Internet Archive capture
`Clinicaltrials.gov identifier: NCT01272232 (Effect of
`Liraglutide on Body Weight in Overweight or Obese
`Subjects With Type 2 Diabetes: SCALE™ - Diabetes)
`May 6, 2011 Internet Archive capture
`Clinicaltrials.gov identifier: NCT00696657 (A
`Randomised Controlled Clinical Trial in Type 2 Diabetes
`Comparing Semaglutide to Placebo and Liraglutide)
`Internet Archive captures
`Clinicaltrials.gov identifier: NCT00294723 (To Evaluate
`the Effect of Liraglutide Versus Glimepiride (Amaryl®)
`on Haemoglobin A1c (LEAD 3)) Internet Archive Capture
`Clinicaltrials.gov identifier: NCT00851773 (Safety,
`Tolerability, and Profile of Action of Drug in the Body of
`NN9535 in Healthy Male Japanese and Caucasian
`Subjects) Internet Archive captures
`Novo Nordisk Company Announcement: Financial report
`for the period 1 January 2018 to 31 March 2018 (dated
`May 2, 2018)
`Ostawal et al., Clinical Effectiveness of Liraglutide in
`Type 2 Diabetes Treatment in the Real-World Setting: A
`Systematic Literature Review, 7 DIABETES THERAPY 411
`(2016)
`Highlights of Prescribing Information: Ozempic,
`Rev. 10/2022
`
`
`
`7
`
`Abbreviation
`Lund
`(EX1035)
`Madsbad
`(EX1111)
`
`Mounjaro label
`(EX1116)
`NCT058
`(1316)
`
`NCT232
`(1317)
`
`NCT657 Protocol
`(EX1013)
`
`NCT723
`(1318)
`
`NCT773
`(EX1014)
`
`Novo Financial
`Report
`(EX1118)
`Ostawal
`(EX1112)
`
`Ozempic® label 2022
`(EX1081)
`
`MPI EXHIBIT 1302 PAGE 7
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`Highlights of Prescribing Information: Ozempic,
`Rev. 9/2023
`Patent and Exclusivity List for: NDA No. N209637
`(Semaglutide – Ozempic) in FDA’s Approved Drug
`Products with Therapeutic Equivalence Evaluations
`(Orange Book) (2024)
`Pi-Sunyer et al., A Randomized, Controlled Trial of 3.0
`mg of Liraglutide in Weight Management, 373 NEW ENG.
`J. MED. 11 (2015)
`Pratley et al., One Year of Liraglutide Treatment Offers
`Sustained and More Effective Glycaemic Control and
`Weight Reduction Compared with Sitagliptin, Both in
`Combination with Metformin, in Patients with Type 2
`Diabetes: A Randomised, Parallel-Group, Open-Label
`Trial, 65 INT’L J. CLINICAL PRACTICE 397 (2011)
`Rubio-Herrera et al., Impact of Treatment with GLP1
`Receptor Agonists, Liraglutide 3.0 mg and Semaglutide
`1.0 mg, While on a Waiting List for Bariatric Surgery, 11
`BIOMEDICINES 2785 (2023)
`Highlights of Prescribing Information: Saxenda,
`Rev. 12/2014
`Approved Drug Products with Therapeutic Equivalence
`Evaluations, Patent and Exclusivity entry for NDA No.
`N206321 (Liraglutide Recombinant – Saxenda) (2018)
`Skrivanek et al., Dose-Finding Results in an Adaptive,
`Seamless, Randomized Trial of Once-Weekly Dulaglutide
`Combined with Metformin in Type 2 Diabetes Patients
`(AWARD-5), 16 DIABETES OBESITY & METABOLISM 748
`(2014)
`Ahmann et al., Efficacy and Safety of Once-Weekly
`Semaglutide Versus Exenatide ER in Subjects with Type 2
`Diabetes (SUSTAIN 3): A 56-Week, Open-Label,
`Randomized Clinical Trial, 41 DIABETES CARE 258
`(2018)
`
`Abbreviation
`Ozempic® label 2023
`(EX2069)
`Ozempic® Orange
`Book
`(EX1101)
`
`Pi-Sunyer
`(EX1125)
`
`Pratley
`(EX1126)
`
`Rubio-Herrera
`(EX1102)
`
`Saxenda label
`(EX1103)
`Saxenda Orange
`Book
`(EX1120)
`Skrivanek
`(EX1113)
`
`SUSTAIN 3
`(EX2085)
`
`
`
`8
`
`MPI EXHIBIT 1302 PAGE 8
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`Aroda et al., Efficacy and Safety of Once-Weekly
`Semaglutide Versus Once-Daily Insulin Glargine as Add-
`On to Metformin (with or without Sulfonylureas) in
`Insulin-Naïve Patients with Type 2 Diabetes (SUSTAIN
`4): A Randomized, Open-Label, Parallel-Group,
`Multicentre, Multinational, Phase 3a Trial, 5 LANCET
`DIABETES & ENDOCRINOLOGY 355 (2017)
`Pratley et al., Semaglutide Versus Dulaglutide Once
`Weekly in Patients with Type 2 Diabetes (SUSTAIN 7): A
`Randomized, Open-Label, Phase 3b Trial, 6 LANCET
`DIABETES & ENDOCRINOLOGY 275 (2018)
`Capehorn et al., Efficacy and Safety of Once-Weekly
`Semaglutide 1.0 mg vs Once-Daily Liraglutide 1.2 mg as
`Add-On to 1-3 Oral Antidiabetic Drugs in Subjects with
`Type 2 Diabetes (SUSTAIN 10), 46 DIABETES &
`METABOLISM 100 (2020)
`Drug Approval Package, Symlin (Pramlintide Acetate)
`Injection, https://www.accessdata.fda.gov/
`drugsatfda_docs/nda/2005/21-332_Symlin.cfm
`(last accessed May 2, 2024).
`Highlights of Prescribing Information: Trulicity,
`Rev. 9/2014
`Vahl, Gut Peptides in the Treatment of Diabetes Mellitus,
`13 EXPERT OPINION ON INVESTIGATIONAL DRUGS 177
`(2004)
`Highlights of Prescribing Information: Victoza,
`Rev. 1/2010
`Approved Drug Products with Therapeutic Equivalence
`Evaluations, Patent and Exclusivity entry for NDA No.
`N022341 (Liraglutide Recombinant (Victoza)) (2011)
`Vilsbøll, Glucagon-Like Peptide-1 and Diabetes
`Treatment, 21 INT’L DIABETES MONITOR 1 (2009)
`Highlights of Prescribing Information: Wegovy®, Rev.
`3/2024
`
`Abbreviation
`SUSTAIN 4
`(EX2083)
`
`SUSTAIN 7
`(EX2084)
`
`SUSTAIN 10
`(EX2082)
`
`Symlin Approval
`Package
`(EX1325)
`
`Trulicity label
`(EX1119)
`Vahl
`(EX1104)
`
`Victoza® label
`(EX1039)
`Victoza® Orange
`Book
`(EX1105)
`Vilsbøll
`(EX1040)
`Wegovy® label
`(EX1106)
`
`
`
`9
`
`MPI EXHIBIT 1302 PAGE 9
`
`

`

`TABLE OF ABBREVIATIONS
`Full Name of Cited Reference
`Patent and Exclusivity List for: NDA No. N215256
`(Semaglutide – Wegovy®) in FDA’s Approved Drug
`Products with Therapeutic Equivalence Evaluations
`(Orange Book) (2024)
`Can Ozempic and Weight-Loss Drugs Treat Other
`Diseases?, NEW YORK TIMES (Dec. 20, 2023)
`White, A Brief History of the Development of Diabetes
`Medications, 27 DIABETES SPECTRUM 82 (2014)
`Khullar, The Year of Ozempic, NEW YORKER (Dec. 14,
`2023)
`
`Abbreviation
`Wegovy® Orange
`Book
`(EX1107)
`
`What’s Next
`(EX2081)
`White
`(EX1108)
`Year of Ozempic
`(EX2080)
`
`
`
`
`
`10
`
`MPI EXHIBIT 1302 PAGE 10
`
`

`

`
`
`1. My name is Allen Spiegel, M.D. I have been retained by Mylan
`
`Pharmaceuticals Inc. (“Mylan”), to provide my expert opinions regarding aspects of
`
`the unpatentability of the claims of U.S. Patent No. 10,335,462 (“’462 patent”).
`
`2.
`
`In this reply declaration, I address and respond to the opinions provided
`
`by Dr. Goland in EX2054, the EXPERT DECLARATION OF ROBIN S. GOLAND, M.D. IN
`
`SUPPORT OF PATENT OWNER’S2 RESPONSE TO PETITION FOR INTER PARTES REVIEW
`
`OF U.S. PATENT NO. 10,335,462 (“Goland Declaration”).
`
`I.
`
`QUALIFICATIONS AND BACKGROUND
`A. Education and Experience; Prior Testimony
`I am the Marilyn & Stanley M. Katz Dean Emeritus, Professor of
`3.
`
`Medicine (Endocrinology) and Professor of Molecular Pharmacology at Albert
`
`Einstein College of Medicine. I have 51 years of experience teaching and
`
`researching treatments for diabetes and metabolic disorders. I have also authored or
`
`co-authored over 412 peer-reviewed articles, reviews, and book chapters covering
`
`basic research on transmembrane signaling and mechanism of hormone action, as
`
`well as translational and clinical research on diagnosis and treatment of
`
`endocrine/metabolic disorders, including identifying the genetic basis for several
`
`endocrine diseases. I edited and coauthored two books on “G proteins, Receptors
`
`
`2 “Patent Owner” refers to the assignee of the ’462 patent, Novo Nordisk A/S.
`
`11
`
`MPI EXHIBIT 1302 PAGE 11
`
`

`

`
`
`and Disease.” I also served as the Associate Editor for Endocrinology Diabetes and
`
`Metabolism for the 25th (2015) and 26th (2019) editions of the Goldman Cecil
`
`Textbook of Medicine. I was U.S. Head of Diabetes and Endocrinology faculty
`
`(2003-2007) for the Faculty of 1000 Medicine Literature Service. I am a diplomate
`
`of the American Board of Internal Medicine and of the subspecialty board on
`
`Endocrinology and Metabolism. I have been a member of the Endocrine Society,
`
`American Society for Biochemistry and Molecular Biology, and the American
`
`Diabetes Association (ADA), having served as chair of the ADA Research
`
`Foundation Council. I hold four U.S. patents and have served on the Scientific
`
`Advisory Board of two biotech companies, Peptimed and Cadus Pharmaceuticals.
`
`Exhibit 1303 is a copy of my curriculum vitae, which provides details of my
`
`education, experiences, and publications.
`
`4.
`
`Prior to my current position, I was at the National Institutes of Health
`
`(NIH) from 1973 to 2006, where I held several positions: Senior Investigator,
`
`Metabolic Diseases Branch, National Institute of Arthritis, Metabolism, and
`
`Digestive Diseases (1977-1984); Chief, Section on Molecular Pathophysiology,
`
`Metabolic Diseases Branch, National Institute of Arthritis, Diabetes and Digestive
`
`and Kidney Diseases (1985-1988); Chief, Molecular Pathophysiology Branch
`
`(1988-1993); Chief, Metabolic Diseases Branch National Institute of Diabetes and
`
`12
`
`MPI EXHIBIT 1302 PAGE 12
`
`

`

`
`
`Digestive and Kidney Diseases (NIDDK) (1993-2000); Scientific Director, Division
`
`of Intramural Research, NIDDK (1990-1999); and Director, NIDDK (1999-2006).
`
`5.
`
`As Director of NIDDK, I served as Co-chair of the NIH Obesity
`
`Research Task Force, and as Chair of the Diabetes Mellitus Interagency
`
`Coordinating Committee (which included representatives from the FDA, CDC,
`
`CMS and VA among others). I was responsible for oversight of major national
`
`clinical trials in diabetes (e.g., the Diabetes Prevention Program) and obesity (e.g.,
`
`Look Ahead). I represented NIDDK/NIH at Town Hall meetings on Diabetes in
`
`Seattle, WA, Little Rock, AR, and Cincinnati, OH, appearing with the Secretary of
`
`the Department of Health and Human Services. I testified on behalf of NIDDK/NIH
`
`at multiple Congressional hearings in the Senate and House related to the NIH
`
`appropriation, human embryonic stem cell research, and type 1 diabetes.
`
`6.
`
`Following my time at the NIH, I was appointed the Marilyn and Stanley
`
`Katz Dean at Albert Einstein College of Medicine from 2006 to 2018. I was the
`
`Executive Vice President and Chief Academic Officer at Montefiore Health System
`
`from 2015 to 2018, and I have served on the Montefiore Health System Board of
`
`Trustees since 2022.
`
`7.
`
`I earned a Bachelor of Arts, summa cum laude, from Columbia
`
`University in 1967 and a Doctor of Medicine, cum laude, from Harvard Medical
`
`School in 1971. I completed my internship at Massachusetts General Hospital in
`
`13
`
`MPI EXHIBIT 1302 PAGE 13
`
`

`

`
`
`Boston, Massachusetts in 1972, and finished my residency at Massachusetts General
`
`Hospital in 1973. From 1973 to 1977, I received my specialized training from the
`
`NIH Endocrinology Training Program as a Clinical Associate in the Metabolic
`
`Diseases Branch of the National Institutes of Health (NIH).
`
`8.
`
`I have been the recipient of a number of honors over my 50 years of
`
`experience, including the Jacobaeus Prize from the Nordisk Insulin Foundation
`
`(1990), Plenary Lecturer from the Japan Endocrine Society (1993), Harrison’s
`
`Memorial Lecture from the Endocrine Society of Australia (1994), Edwin B.
`
`Astwood Lecture Award from the Endocrine Society (1998), election to the National
`
`Academy of Medicine (formerly the Institute of Medicine of the National
`
`Academies) (2002), Esoterix Lecture Award from the Lawson Wilkins Pediatric
`
`Endocrine Society (2003), and Priscilla White Lecturer from the Joslin Diabetes
`
`Center-Harvard Medical School (2004).
`
`9.
`
`In the previous four years, I have not provided testimony in any legal
`
`proceeding.
`
`Basis of Opinions and Materials Considered
`B.
`10. Appendix A includes a list of the materials I considered, in addition to
`
`my experience, education, and training, to provide the opinions contained in this
`
`declaration.
`
`14
`
`MPI EXHIBIT 1302 PAGE 14
`
`

`

`
`
`C. Retention and Compensation
`11. Mylan retained me as a technical expert to provide various opinions
`
`about the ’462 patent. I am being compensated at a rate of $1,500 per hour plus
`
`expenses for this work. My compensation is in no way tied to the outcome of this
`
`proceeding or to the content of this declaration, and it has not altered my opinions.
`
`II.
`
`SUMMARY OF OPINIONS
`In my opinion, the Goland Declaration fails to establish that secondary
`12.
`
`considerations evidence weighs in favor of finding the claims of the ’462 patent
`
`patentable.
`
`13. First, the Goland Declaration suffers from several overarching
`
`deficiencies that affect its conclusions.
`
`14. For example, the Goland Declaration generally failed to compare the
`
`’462 patent’s claimed semaglutide once weekly 1.0 mg dosing regimen to the closest
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`prior art where I understand that the law requires it.
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`15. Further, the Goland Declaration also failed to support much of its
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`reasoning with testable evidence, often asserting broad swaths of opinion as fact,
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`unmoored from any underlying documentary evidence.
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`16. Finally, the Goland Declaration erroneously suggested that the use of
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`Ozempic® according to its label has a nexus with the ’462 patent’s claimed
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`semaglutide once weekly 1.0 mg dosing regimen, when, in fact, most of the uses on
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`the Ozempic® label do not fall within the scope of the claims of the ’462 patent.
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`17.
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`Second, the Goland Declaration failed to establish on the merits the
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`asserted secondary considerations.
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`18. For example, the Goland Declaration failed to establish with relevant
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`evidence that the inventions claimed in the ’462 patent yielded unexpected results.
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`19. And, the Goland Declaration failed to establish with relevant evidence
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`that the inventions claimed in the ’462 patent satisfied a long-felt but unmet need in
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`the art.
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`20.
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`In addition, the Goland Declaration failed to establish with relevant
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`evidence that the inventions claimed in the ’462 patent have been the subject of
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`praise.
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`21. Finally, the Goland Declaration failed to establish with relevant
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`evidence that there was skepticism toward the inventions claimed in the ’462 patent.
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`III. LEGAL STANDARDS
`22. To prepare and form my opinions set forth in this declaration, I have
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`been informed of certain applicable legal principles. I applied my understanding of
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`those principles in forming my opinions. My understanding of those principles is
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`summarized below.3 I took these principles into account when forming my opinions
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`in this case.
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`23.
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`I have been informed that Mylan contends that the ’462 patent is
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`unpatentable because the prior art anticipated and rendered obvious the claims of the
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`’462 patent.
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`24.
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`I have been informed that Mylan bears the burden of proving
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`unpatentability by a preponderance of the evidence. I have been told that this means
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`the Board, considering the evidence, must find it more likely than not that the claims
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`of the ’462 patent are unpatentable.
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`25.
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`I understand that my opinions regarding unpatentability are presented
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`from the viewpoint of a person of ordinary skill in the art (POSA) in the field of
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`technology of the patent as of the patent’s priority date.
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`3 As support for my analysis and to help me reach my opinions and conclusions, I
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`was informed of and advised to apply various legal principles relating to
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`unpatentability, which I set forth here. By setting forth these legal standards, here
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`and below, I do not intend to testify about the law. I only provide my understanding
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`of the law, as explained to me by counsel, as a context for the opinions and
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`conclusions I provide. I generally flag a provided legal rule or assumption using
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`language like “I understand,” “my understanding,” or “I am informed.”
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`26.
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`It is my understanding that a patent claim is invalid for anticipation if a
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`prior art reference disclosed all elements of that claim expressly and/or inherently as
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`arranged in the claim.
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`27.
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`It is my understanding that a patent is unpatentable for obviousness if
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`the differences between the claimed invention and the prior art are such that the
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`claimed invention as a whole would have been obvious to a POSA. I have also been
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`informed that obviousness is a legal question based on certain underlying factual
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`determinations. Among the factual determinations are (1) the scope and content of
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`the prior art; (2) the differences between the claimed invention and the prior art; (3)
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`the level of ordinary skill in the art; and (4) secondary considerations of
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`nonobviousness.
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`28.
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`I understand that the secondary considerations4 used to determine the
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`obviousness of claimed subject matter may include evidence of such things as
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`unexpected results over the prior art, commercial success, long-felt but unsolved
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`needs, skepticism, praise, failure of others, etc., and that secondary considerations,
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`to the extent they are offered by the Patent Owner, should be considered.
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`29.
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`It is also my understanding that while Mylan always bears the ultimate
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`burden of persuasion on obviousness, it is the Patent Owner who bears the burden
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`4 I understand that these may also be referred to as “objective indicia.”
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`of production with respect
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`to evidence of secondary considerations of
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`nonobviousness.
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`30.
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`I also understand that for evidence to support secondary considerations,
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`the evidence must have a nexus to the patent claims. It is my understanding that
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`nexus means there must be a sufficient legal and factual connection between the
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`evidence and the patented invention to afford the consideration substantial weight. I
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`have been informed that where secondary considerations result from something
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`other than what is both claimed and novel in the claim, there is no nexus to the merits
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`of the claimed invention.
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`31.
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`It is also my understanding that the patentee bears the burden of
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`showing that a nexus exists, and that a Patent Owner may be entitled a rebuttable
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`presumption of nexus when the evidence is tied to a specific product and the product
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`embodies the claimed invention and is coextensive with it. That is, the evidence must
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`be commensurate in scope with the claims. While perfect correspondence is not
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`required, the Patent Owner must demonstrate the product is essentially the claimed
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`invention. I also understand that even where a presumption of nexus is inappropriate,
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`the Patent Owner is still afforded an opportunity to prove nexus by showing that the
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`evidence of secondary considerations is the direct result of the unique characteristics
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`of the claimed invention.
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`32. Further, it is my understanding that there is no presumption of nexus to
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`a patent when a product is covered by more than one patent, particularly when the
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`evidence of secondary considerations relates to a second patent but a first,
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`“blocking,” patent exists. I also understand that where a product embodies claims
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`from two patents, a presumption of nexus can be appropriate only if the claims of
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`both patents generally cover the same invention. It is my understanding that a patent
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`claim is not coextensive with a product that includes a critical unclaimed feature that
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`is claimed by a different patent and that materially impacts the product’s
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`functionality.
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`33.
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`I understand that evidence of long felt, yet unmet need in the industry
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`for the product covered by the invention may support the invention was not obvious.
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`But it is my understanding that long felt need cannot be presumed, and must be
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`proven. Further, it is my understanding that for a long felt, unmet need to support an
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`invention as not being obvious, the need must be filled by the features of the claimed
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`invention and not simply disclosed in the specification.
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`34.
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`I understand that for a Patent Owner to establish unexpected results, the
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`Patent Owner must demonstrate that there is a difference between the results
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`produced by the alleged invention and those produced by the closest prior art, and
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`that the results would have been unexpected by a POSA considering the prior art at
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`the time of the invention.
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`35.
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`I also understand that for unexpected results to be persuasive, the new
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`and unexpected results produced by the claimed invention must be different in kind,
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`and not merely in degree, from the results produced by the prior art. I understand
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`that a difference in kind can be the presence of a new property dissimilar to the
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`known property from the prior art.
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`36.
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`I also understand that the evidence of unexpected results must be
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`commensurate in scope with the claims which the evidence is offered to support.
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`37.
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`I also understand that a Patent Owner relying on unexpected results to
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`rebut a prima facie case of obviousness must compare the claimed invention to the
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`closest prior art.
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`38.
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`It is also my understanding that secondary considerations based on
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`skepticism must both 1) have a nexus with the claimed invention, and 2) not be
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`purely from unsubstantiated arguments by experts or interested parties, which are
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`given little weight.
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`39.
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`It is my understanding that for industry praise to weigh against
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`obviousness it must be specifically directed at the claimed invention. But when
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`praise is linked to claim elements already known in the prior art, or is unconnected
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`to the elements, this secondary consideration is given little weight.
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`IV. PERSON OF ORDINARY SKILL IN THE ART
`I understand that I am to present my opinions regarding unpatentability
`40.
`
`of the claims from the point of view of a person of ordinary skill in the art (“POSA”)
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`in the field of technology of the patent as of the invention date.
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`41.
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`I understand that several nonexhaustive factors may be considered to
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`determine the level of ordinary skill in the art, including “(1) the educational level
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`of the inventor; (2) type of problems encountered in the art; (3) prior art solutions to
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`those problems; (4) rapidity with which innovations are made; (5) sophistication of
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`the technology; and (6) educational level of active workers in the field.”
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`42.
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`I understand that, earlier in this proceeding, Mylan proposed a
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`definition for a person of ordinary skill in the art for purposes of the ’462 patent,
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`presented below. I agree with this definition. I reserve the right to amend and/or
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`supple