`
`IN THE UNITED STATES DISTRICT COURT
`
`FOR THE DISTRICT OF DELAWARE
`
`No. 22-md-3038-CFC
`
`No. 22-cv-294-CFC
`CONSOLIDATED
`ANDA CASE
`
`No. 22-cv-1040-CFC
`ANDA CASE
`
`IN RE: OZEMPIC (SEMAGLUTIDE)
`PATENT LITIGATION
`
`
`
`NOVO NORDISK INC. and NOVO
`NORDISK A/S,
`
`Plaintiffs/Counterclaim
`Defendants,
`
`v.
`
`
`RIO BIOPHARMACEUTICALS INC. et al.,
`
`Defendants/Counterclaim
`Plaintiffs.
`
`
`
`NOVO NORDISK INC. and NOVO
`NORDISK A/S,
`
`Plaintiffs/Counterclaim
`Defendants,
`
`v.
`
`
`MYLAN PHARMACEUTICALS INC.,
`
`Defendant/Counterclaim
`Plaintiff.
`
`
`
`Opening Expert Report of Dr. John Bantle
`Regarding Invalidity of U.S. Patent No. 10,335,462
`
`
`
`Novo Nordisk Exhibit 2537
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00001
`
`

`

`TABLE OF CONTENTS
`
`
`Page
`
`
`I.
`
`Qualifications and Background ........................................................... 1
`A. Education and Experience; Prior Testimony .............................. 1
`B.
`Basis for Opinions and Materials Considered ............................. 4
`C. Retention and Compensation .................................................... 4
`Summary of Opinions ........................................................................ 4
`II.
`III. Legal Standards ................................................................................. 7
`IV. Person of Ordinary Skill in the Art ...................................................... 9
`V.
`The ’462 Patent and Its Asserted Claims ........................................... 11
`VI. Claim Construction .......................................................................... 19
`VII. Background on Diabetes and the use of GLP-1 Derivatives for the
`Treatment of Diabetes ...................................................................... 20
`A. Diabetes Generally ................................................................. 20
`B. Diabetes Treatment ................................................................. 22
`C. The Use of GLP-1 Derivatives to Treat Diabetes ...................... 25
`D. Use of Liraglutide to Treat Diabetes ........................................ 27
`E.
`Extended-Use GLP-1 Receptor Agonists ................................. 32
`VIII. Scope and Content of the Prior Art ................................................... 41
`A. Lovshin .................................................................................. 43
`B. Madsbad ................................................................................ 45
`C. U.S. Patent No. 8,114,833 ....................................................... 47
`D. WO 2006/097537 ................................................................... 54
`E. WO 2011/138421 ................................................................... 60
`F. NCT00696657 Semaglutide Clinical Trial Record .................... 64
`1.
`Clinical Trial No. NCT00696657 ................................... 64
`2.
`ClinicalTrials.gov is a Part of the POSA’s Knowledge ..... 66
`G. Other Technical Background Forming the POSA’s
`Knowledge ............................................................................. 73
`
`ii
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`

`

`
`
`IX.
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`Clinical Trial No. NCT00851773 ................................... 73
`1.
`Bhansali ........................................................................ 79
`2.
`3. Drucker 2003 ................................................................. 84
`4. Holst 2004 ..................................................................... 85
`5. Knudsen 2001 ............................................................... 89
`6. Knudsen 2004 ............................................................... 93
`7. Knudsen patent (U.S. Patent No. 6,268,343) ................... 98
`8.
`Lund ............................................................................ 103
`9. U.S. Patent Application Pub. No. US2007/0010424 ...... 103
`10. Victoza label ................................................................. 108
`11. WO 03/002136 ............................................................ 111
`12. Additional prior art and references ................................ 116
`Invalidity of the Asserted Claims of the ’462 Patent .......................... 117
`A. Each of WO ’421, NCT00696657, and Lovshin anticipated
`claims 1 and 3 ........................................................................ 117
`1. WO ’421 ...................................................................... 118
`2. NCT00696657 .............................................................. 126
`3.
`Lovshin ........................................................................ 133
`B. All Asserted Claims of the ’462 Patent Would Have Been
`Obvious Over the Prior Art .................................................... 141
`1.
`Claims 1, 3, 4, 5, and 7 of the ’462 patent would have
`been obvious over WO ’421, NCT00696657, WO ’537
`and/or Lovshin, optionally in view of one or more of
`the ’833 Patent and Madsbad ........................................ 142
`Claims 1, 3, 4, 5, and 7 of the ’462 patent would have
`been obvious over WO ’421 alone or in view of the
`’833 patent ................................................................... 168
`Claims 1, 3, 4, 5, and 7 of the ’462 patent would have
`been obvious over WO ’537 in view of Lovshin ............. 181
`
`3.
`
`2.
`
`iii
`
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`
`

`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`C. All Claims of the ’462 Patent Are Invalid for Lack of
`Written Description if They Would not have been Obvious ..... 194
`X. Reservation of Rights ...................................................................... 202
`
`iv
`
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`

`

`
`
`
`
`
`TABLE OF ABBREVIATIONS
`
`Full Name of Cited Reference
`U.S. Patent Application Pub. No. US2011/0166321
`U.S. Patent Application Pub. No. US2007/0010424
`U.S. Patent No. 10,335,462
`NN-OZEM-000000071-95
`U.S. Patent No. 10,335,462 file history
`NN-OZEM-000003820-4446
`U.S. Patent No. 5,512,549
`U.S. Patent No. 8,114,833
`SEMA(JDG)_0000447-468
`Banting, The Internal Secretion of the Pancreas, 7 J. LAB.
`CLINICAL MED. 251 (1922)
`Bell, Hamster Preproglucagon Contains the Sequence of Glucagon
`and Two Related Peptides, 302 NATURE 716 (1983)
`Bhansali, Historical Overview of Incretin Based Therapies, 58 J.
`ASSOC. OF PHYSICIANS OF INDIA 10 (2010)
`SEMA(JDG)_0000014-18
`Highlights of Prescribing Information: Bydureon, Rev.
`1/2012
`https://www.accessdata.fda.gov/drugsatfda_docs/label/20
`12/
`022200Orig1s000lbledt.pdf (last accessed Feb. 26, 2024)
`Highlights of Prescribing Information: Byetta, Rev.
`10/2009
`https://www.accessdata.fda.gov/drugsatfda_docs/label/20
`09/
`021773s9s11s18s22s25lbl.pdf (last accessed Feb. 26, 2024)
`ClinicalTrials.gov Background, CLINICALTRIALS.GOV,
`https://clinicaltrials.gov/about-site/about-ctg (last visited
`Mar. 15, 2024)
`
`Abbreviation
`’321 publication
`’424 publication
`’462 patent
`
`’462 file history
`
`’549 patent
`’833 patent
`
`Banting
`
`Bell
`
`Bhansali
`
`Bydureon label
`
`Byetta label
`
`ClinicalTrials.g
`ov Background
`
`5
`
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`
`

`

`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Drab, Incretin-Based Therapies for Type 2 Diabetes Mellitus:
`Current Status and Future Prospects, 30 PHARMACOTHERAPY
`609 (2010)
`Drucker, Enhancing Incretin Action for the Treatment of Type 2
`Diabetes, 26 DIABETES CARE 2929 (2003)
`Drucker, The Incretin System: Glucagon-Like Peptide-1 Receptor
`Agonists and Dipeptidyl Peptidase-4 Inhibitors in Type 2
`Diabetes, 368 LANCET 1696 (2006)
`Drucker, The Biology Of Incretin Hormones, 3 CELL
`METABOLISM 153 (2006)
`Glaesner, Engineering and Characterization of the Long-Acting
`Glucagon-Like Peptide-1 Analogue LY2189265, an Fc Fusion
`Protein, 26 DIABETES/METABOLISM RSCH. & REV. 287
`(2010)
`HARRISON’S PRINCIPLES OF INTERNAL MED., Chapter 338
`(Fauci et al. eds. 17th ed. 2008)
`Award: ClinicalTrials.gov,
`https://ash.harvard.edu/news/clinicaltrialsgov (last visited
`Mar. 15, 2024)
`Holst, Truncated Glucagon-like Peptide I, an Insulin-Releasing
`Hormone from the Distal Gut, 211 FEBS LETTERS 169 (1987)
`Holst, Glucagon-Like Peptide 1 and Inhibitors of Dipeptidyl
`Peptidase IV in the Treatment of Type 2 Diabetes Mellitus, 4
`CURRENT OP. IN PHARMACOLOGY 589 (2004)
`Jimenez-Solem, Dulaglutide, a Long-Acting GLP-1 Analog
`Fused with an Fc Antibody Fragment for the Potential Treatment
`of Type 2 Diabetes, 12 CURRENT OP. IN MOLECULAR
`THERAPEUTICS 790 (2010)
`Kim, Effects of Once-Weekly Dosing of a Long-Acting Release
`Formulation of Exenatide on Glucose Control and Body Weight in
`Subjects with Type 2 Diabetes, 30 DIABETES CARE 1487 (2007)
`SEMA(JDG)_0002583-2589
`
`Abbreviation
`Drab
`
`Drucker 2003
`
`Drucker 2006a
`
`Drucker 2006b
`
`Glaesner
`
`Harrison’s
`
`Harvard Award
`
`Holst 1987
`
`Holst 2004
`
`Jimenez-Solem
`
`Kim
`
`6
`
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`
`

`

`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Knudsen, GLP-1 Derivatives as Novel Compounds for the
`Treatment of Type 2 Diabetes: Selection of NN2211 for Clinical
`Development, 26 DRUGS OF THE FUTURE 677 (2001)
`Knudsen, Glucagon-like Peptide-1: The Basis of a New Class of
`Treatment for Type 2 Diabetes, 47 J. MED. CHEMISTRY 4128
`(2004)
`Knudsen, Liraglutide, a GLP-1 Analogue to Treat Diabetes in
`ANALOGUE-BASED DRUG DISCOVERY II (Fischer &
`Ganellin eds. 2010)
`Knudsen, Liraglutide: The Therapeutic Promise from Animal
`Models, 64 INT’L J. CLINICAL PRACTICE 4 (2010)
`U.S. Patent No. 6,268,343
`SEMA(JDG)_0000487-624
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes Mellitus,
`5 NATURE REV. ENDOCRINOLOGY 262 (2009)
`SEMA(JDG)_0002250-58
`Lund, Emerging GLP-1 Receptor Agonists, 16 EXPERT OP. ON
`EMERGING DRUGS 607 (2011)
`Madsbad, An Overview of Once-Weekly Glucagon-Like Peptide-1
`Receptor Agonists—Available Efficacy and Safety Data and
`Perspectives for the Future, 13 DIABETES, OBESITY &
`METABOLISM 394 (2011)
`SEMA(JDG)_0002439-52
`Marre, GLP-1 Receptor Agonists Today, 93 DIABETES RSCH. &
`CLINICAL PRAC. 317 (2011)
`Mojsov, Insulinotropin: Glucagon-like Peptide I (7-37) Co-
`encoded in the Glucagon Gene is a Potent Simulator of Insulin
`Release in the Perfused Rat Pancreas, 79 J. CLIN. INVEST. 616
`(1987)
`Monami, Effects of Glucagon-Like Peptide-1 Receptor Agonists
`on Body Weight: A Meta-Analysis, 2012 EXPERIMENTAL
`DIABETES RSCH. 1 (2012)
`
`Abbreviation
`Knudsen 2001
`
`Knudsen 2004
`
`Knudsen 2010a
`
`Knudsen 2010b
`
`Knudsen patent
`
`Lovshin
`
`Lund
`
`Madsbad
`
`Marre
`
`Mojsov
`
`Monami
`
`7
`
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`

`

`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`NCT00167115, CLINICALTRIALS.GOV,
`https://www.clinicaltrials.gov/ct2/show/NCT00167115
`(last visited Mar. 15, 2024)
`NCT01933490, CLINICALTRIALS.GOV,
`https://www.clinicaltrials.gov/ct2/show/NCT01933490
`(last visited Mar. 15, 2024)
`Clinical Trial No. NCT00696657
`Clinical Trial No. NCT00851773
`Nielsen, Pharmacology of Exenatide (Synthetic Exendin-4): A
`Potential Therapeutic for Improved Glycemic Control of Type 2
`Diabetes, 117 REGUL. PEPTIDES 77 (2004)
`Novo Nordisk Pipeline – Semaglutide (2010-2011)
`http://novonordisk.com:80/science/pipeline
`/rd_pipeline.asp?showid=7 (Internet Archive captures)
`Seino, Dose-Dependent Improvement in Glycemia with Once-
`Daily Liraglutide without Hypoglycemia or Weight Gain: A
`Double-Blind, Randomized, Controlled Trial in Japanese Patients
`with Type 2 Diabetes, 81 DIABETES RSCH. & CLINICAL
`PRACTICE 161 (2008)
`Tamimi, Drug Development: From Concept to Marketing!, 113
`NEPHRON CLINICAL PRACTICE c125 (2009)
`Tasneem, The Database for Aggregate Analysis of
`ClinicalTrials.gov (AACT) and Subsequent Regrouping by
`Clinical Specialty, 7(3) PLOS ONE 1 (2012)
`Victoza, PHYSICIANS’ DESK REFERENCE (65th ed. 2011)
`Vilsbøll, Glucagon-Like Peptide-1 and Diabetes Treatment, 21
`INTERNATIONAL DIABETES MONITOR 1 (2009)
`Int’l Patent Application Pub. No. WO 03/002136
`SEMA(JDG)_0000373-422
`Int’l Patent Application Pub. No. WO 2011/058193
`Int’l Patent Application Pub. No. WO 2011/073328
`
`Abbreviation
`NCT00167115
`
`NCT01933490
`
`NCT00696657
`NCT00851773
`Nielsen
`
`Novo Pipeline
`
`Seino
`
`Tamimi
`
`Tasneem
`
`Victoza label
`Vilsbøll
`
`WO ’136
`
`WO ’193
`WO ’328
`
`8
`
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`

`

`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Int’l Patent Application Pub. No. WO 2011/138421
`SEMA(JDG)_0002087-2158
`Int’l Patent Application Publication No. WO 91/11457
`Int’l Patent Application Pub. No. WO 2006/097537
`SEMA(JDG)_0002453-2528
`Zarin, The ClinicalTrials.gov Results Database—Update and
`Key Issues, 364 NEW ENGL. J. MED. 852 (2011)
`
`Abbreviation
`WO ’421
`
`WO ’457
`WO ’537
`
`Zarin
`
`
`
`
`
`
`
`9
`
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`

`

`
`
`
`1. My name is John P. Bantle, M.D. I have been retained by Mylan
`
`Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s
`
`Laboratories, Inc., Rio Biopharmaceuticals Inc. and EMS S/A; Sun
`
`Pharmaceutical Industries Ltd. and Sun Pharmaceutical Industries, Inc.; and
`
`Zydus Worldwide DMCC, Zydus Pharmaceuticals (USA) Inc., and Zydus
`
`Lifesciences Limited (collectively, “defendants”), to provide my expert opinions
`
`regarding the invalidity of the asserted claims of U.S. Patent No. 10,335,462
`
`(“’462 patent”), which I understand to be claims 1, 3, 4, 5, and 7.
`
`I. QUALIFICATIONS AND BACKGROUND
`A. Education and Experience; Prior Testimony
`2.
`I am a medical endocrinologist and Professor Emeritus of Medicine
`
`in the Division of Endocrinology and Diabetes, Department of Medicine, at the
`
`University of Minnesota. I have substantial experience in clinical research,
`
`treatment of patients, and academic publications in the field of the treatment of
`
`diabetes and related conditions.
`
`3.
`
`I earned a Bachelor of Science degree in 1970 from the University
`
`of Minnesota and a Doctor of Medicine degree in 1972 from the University of
`
`Minnesota Medical School. I completed an
`
`internship at Cleveland
`
`Metropolitan General Hospital in 1973; residencies in internal medicine at the
`
`Mayo Clinic in Rochester, Minnesota, and Dunedin Public Hospital in
`
`1
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`
`
`Dunedin, New Zealand, in 1975 and 1976, respectively; and a fellowship in
`
`endocrinology and metabolism at the University of Minnesota in 1978. I was a
`
`long-time medical practitioner in Minnesota, and earned board certifications
`
`from the American Board of Internal Medicine and in Endocrinology and
`
`Metabolism.
`
`4.
`
`For nearly 40 years, I was an instructor, assistant professor,
`
`associate professor, and then full professor, in the Department of Medicine of
`
`the University of Minnesota Medical School. Since 2017, I have held the
`
`position of Professor Emeritus at the medical school. I also held significant
`
`administrative and research positions: I was the Associate Director of the
`
`General Clinical Research Center at the University of Minnesota Medical
`
`School from 1983-2009, the Medical Staff Clinical Service Chief for Internal
`
`Medicine at Fairview-University Medical Center from 2001-2007, and the
`
`Clinical Research Implementation Services Leader of the Clinical and
`
`Translational Science Institute at the University of Minnesota from 2011-2013.
`
`Finally, I was the Interim Director and then the full Director of the Division of
`
`Endocrinology and Diabetes in the Department of Medicine at the University
`
`of Minnesota Medical School from 2008 to 2015.
`
`5.
`
`I participated in numerous clinical trials, both as principal
`
`investigator and co-investigator, and remained current on treatment methods for
`
`2
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`
`
`patients with diabetes, including developing nutritional recommendations for
`
`people with diabetes and developing the national standards of care for diabetes
`
`patients.
`
`6.
`
`I have authored approximately 120 publications and book chapters,
`
`and made numerous presentations on the topic of diabetes at national and
`
`international medical meetings.
`
`7.
`
`I have received numerous honors and awards for my teaching,
`
`clinical excellence, and treatment of patients. For example, I was selected by my
`
`peers to be named by the Best Doctors Organization as one of the Best Doctors
`
`in America for twenty-two consecutive years from 1996-2017; I was named a
`
`Top Doctor by Minneapolis/St. Paul Magazine in 1992, 1994, 1996, 1999-2002,
`
`2004, and 2006-2017; and I received the University of Minnesota Department
`
`of Medicine Clinical Excellence Award in 2002, 2004, and 2011.
`
`8.
`
`In the previous four years, I have provided testimony in the
`
`following proceedings:
`
`• Boehringer Ingelheim Pharms. Inc. v. Mankind Pharma Ltd.,
`No. 18-cv-01689 (D. Del.);
`
`• Janssen, Inc., Janssen Oncology, Inc. and BTG Int’l LTD v. Dr. Reddy’s
`Labs. Ltd., Dr. Reddy’s Labs., Inc. and Pharmascience, Inc., T-978-19
`(Ottawa, Ontario); and
`
`• Mylan Pharmaceuticals Inc. v. Novo Nordisk A/S, No. IPR2023-00724
`(P.T.A.B.).
`
`3
`
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`
`9. My qualifications are further described on my curriculum vitae,
`
`attached as Exhibit A.
`
`B. Basis for Opinions and Materials Considered
`10. Exhibit B includes a list of the materials I considered, in addition to
`
`my experience, education, and training, to provide the opinions contained in
`
`this report.
`
`C. Retention and Compensation
`11. Defendants retained me as a technical expert to provide various
`
`opinions about the ’462 patent. I am being compensated at a rate of $400 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 report, and it has not altered
`
`my opinions.
`
`II.
`
`SUMMARY OF OPINIONS
`
`12. My opinions are limited to the treatment of diabetes with
`
`semaglutide, as claimed in the ’462 patent. I present my opinions from the
`
`perspective of a POSA who is a medical doctor.
`
`13. Based on my view of the prior art, it is my opinion that the claims
`
`of the ’462 patent would have been anticipated by or obvious over the following
`
`references or combinations of references:
`
`a) WO ’421 anticipated claims 1-3 of the ’462 patent;
`
`4
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`b) NCT00696657 anticipated claims 1 and 3 of the ’462 patent;
`
`c) Lovshin anticipated claims 1 and 3 of the ’462 patent;
`
`d) Claims 1, 3, 4, 5, and 7 of the ’462 patent would have been obvious
`
`over WO ’421, NCT00696657, WO ’537, and/or Lovshin,
`
`optionally in view of one or more of the ’833 Patent and Madsbad;
`
`e) Claims 1, 3, 4, 5, and 7 of the ’462 patent would have been obvious
`
`over WO ’421 alone or in view of the ’833 Patent;
`
`f) Claims 1, 3, 4, 5, and 7 of the ’462 patent would have been obvious
`
`over WO ’537 in view of Lovshin.
`
`14. As detailed below, WO ’421, NCT00696657, and Lovshin disclosed
`
`all the limitations recited in claims 1 and 3 of the ’462 patent.
`
`15. However, to the extent the Court in this case finds that WO ’421,
`
`NCT00696657, and Lovshin each did not anticipate claims 1 and 3 of the ’462
`
`patent, then, in light of the state of the art, WO ’421, NCT00696657, WO ’537,
`
`and Lovshin each would have rendered obvious claims 1, 3, 4, 5, and 7 of the
`
`’462 patent because each reference would have motivated a skilled artisan to
`
`treat diabetes with a once weekly, 1.0 mg semaglutide injectable formulation
`
`with a reasonable expectation of success doing so, alone or in view of the ’833
`
`patent and Madsbad.
`
`5
`
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`16. Additionally, both WO ’421 in view of the ’833 patent and WO ’537
`
`in view of Lovshin would have motivated a skilled artisan to treat diabetes with
`
`a once weekly, 1.0 mg semaglutide injectable formulation with a reasonable
`
`expectation of success doing so, rendering obvious claims 1, 3, 4, 5, and 7 of the
`
`’462 patent.
`
`17.
`
`I understand that defendants’ expert Dr. Paul Dalby is submitting
`
`an expert report and offering his opinions that it would have been obvious over
`
`the prior art for a POSA to formulate semaglutide as claimed in dependent
`
`claims 4, 5, and 7 of the ’462 patent. I defer to Dr. Dalby’s opinions regarding
`
`the obviousness of these claims of the ’462 patent.
`
`18. Finally, it is my opinion that the ’462 patent is invalid for a lack of
`
`adequate written description of the subject matter claimed in claims 1, 3, 4, 5,
`
`and 7 because the patent specification does not inform a person of ordinary skill
`
`in the art that the inventors actually possessed a method for treating type 2
`
`diabetes comprising administering semaglutide once weekly in an amount of 1.0
`
`mg to a subject in need thereof.
`
`19.
`
`I understand that Plaintiffs Novo Nordisk Inc. and Novo Nordisk
`
`A/S may present expert opinions regarding “secondary considerations” of
`
`nonobviousness of the method of treatment claims, and/or of other claims, in
`
`response to my report, and that I may be asked to address such opinions in the
`
`6
`
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`
`future. I therefore expressly reserve the right to address later all issues of
`
`secondary considerations that Plaintiffs’ experts may raise.
`
`III. LEGAL STANDARDS
`20. To prepare and form my opinions set forth in this report, I have been
`
`informed of the relevant legal principles. I applied my understanding of those
`
`principles in forming my opinions. My understanding of those principles is
`
`summarized below.1 I took these principles into account when forming my
`
`opinions in this case.
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`21.
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`I have been informed that the defendants bear the burden of proving
`
`invalidity by clear and convincing evidence. I have been told that this means the
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`Court, considering the evidence, must have an abiding conviction that it is
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`highly probable that the asserted claims are invalid.
`
`
`1 As support for my analysis and to help me reach my opinions and conclusions,
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`I was informed of and advised to apply various legal principles relating to
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`invalidity, which I set forth here. By setting forth these legal standards, here and
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`below, I do not intend to testify about the law. I only provide my understanding
`
`of the law, as explained to me by counsel, as a context for the opinions and
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`conclusions I provide.
`
`7
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`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00016
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`22.
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`I understand that my opinions regarding invalidity are presented
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`from the viewpoint of a person of ordinary skill in the art (“POSA”) in the field
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`of technology of the patent as of the patent’s priority date.
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`23.
`
`I am told that for a patent to be anticipated, a prior art reference
`
`must disclose all elements of that claim expressly and/or inherently as arranged
`
`in the claim.
`
`24.
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`I am told that the concept of patent obviousness involves four
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`factual inquiries: (1) the scope and content of the prior art; (2) the differences
`
`between the claimed invention and the prior art; (3) the level of ordinary skill in
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`the art; and (4) secondary considerations of nonobviousness.
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`25.
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`I understand that when there is some recognized reason to solve a
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`problem, and there are a finite number of identified, predictable and known
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`solutions, a person of ordinary skill in the art has good reason to pursue the
`
`known options within his or her technical grasp. If such an approach leads to
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`the expected success, it is likely not the product of innovation but of ordinary
`
`skill and common sense. I understand that any need or problem known in the
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`field of endeavor at the time of invention or addressed by the patent can provide
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`a reason for combining prior art elements to arrive at the claimed subject matter.
`
`I understand that only a reasonable expectation of success is necessary to show
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`obviousness.
`
`8
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`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00017
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`26.
`
`I understand that there is a presumption of obviousness where a
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`claimed invention overlaps with or falls within a range disclosed in the prior art.
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`27.
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`I understand that for a patent to be valid, the patent specification
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`must contain a written description of the claimed invention.
`
`28.
`
`I understand that determining whether a patent specification
`
`contains an adequate written description of the invention requires an objective
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`inquiry into the complete specification from the perspective of a person of
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`ordinary skill in the art. Based on that inquiry, the specification must describe
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`the invention in a way understandable to the person of ordinary skill in the art
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`and show that the inventor actually invented the invention claimed.
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`29.
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`I understand that a specification does not provide an adequate
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`written description of the invention if it only renders the claimed invention
`
`obvious when considering the provided description.
`
`IV. PERSON OF ORDINARY SKILL IN THE ART
`30.
`In my opinion, the following definition of a person of ordinary skill
`
`in the art applies to the claims of the ’462 patent. I reserve the right to amend
`
`and/or supplement my opinions on invalidity if the Court adopts, or the parties
`
`agree to, a different definition of a skilled artisan.
`
`31. The subject matter of claims 1, 3, 4, 5 and 7 of the ’462 patent falls
`
`within the medicinal chemical arts. A skilled artisan would have had (1) an
`
`9
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`Novo Nordisk Exhibit 2537
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00018
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`

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`M.D., a Pharm.D., or a Ph.D.
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`in pharmacy, chemical engineering,
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`bioengineering, chemistry, or related discipline; (2) at least two years of
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`experience in protein or peptide therapeutic development and/or manufacturing
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`or diabetes treatments; and/or (3) experience with the development, design,
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`manufacture, formulation, or administration of therapeutic agents, and the
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`literature concerning protein or peptide formulation and design, or diabetes
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`treatments.
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`32. Alternatively, the skilled artisan would be (1) a highly skilled
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`scientist lacking an M.D., a Pharm.D., or a Ph.D., but would have (2) more than
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`five years of experience in protein or peptide therapeutic development and/or
`
`manufacturing or diabetes treatments; and/or (3) experience with the
`
`development, design, manufacture,
`
`formulation, or administration of
`
`therapeutic agents for diabetes, and the literature concerning protein or peptide
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`formulation and design, or diabetes treatments.
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`33. A skilled artisan would have understood the prior art references
`
`referred to herein and would have the capability to draw inferences. It is
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`understood that, to the extent necessary, a skilled artisan may collaborate with
`
`one or more other skilled artisans for one or more aspects with which the other
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`skilled artisan may have expertise, experience, and/or knowledge. Additionally,
`
`10
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`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00019
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`

`

`
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`a skilled artisan could have had a lower level of formal education than what I
`
`describe here if the person has a higher degree of experience.
`
`34.
`
`I understand that Plaintiffs proposed that a person of ordinary skill
`
`in the art would have, among other possible qualifications, an M.D., Ph.D. or
`
`equivalent degree in Pharmacology, Pharmaceutics, Biopharmaceutics, or a
`
`related field, and 3-5 years of experience conducting clinical research in the field
`
`of diabetes treatments, including the design of dosing regimens and dosage
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`forms for type 2 diabetes treatments, or 3-5 years of research or industry
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`experience relating to developing pharmaceutical formulations.
`
`35. As explained in this report and exemplified by the information
`
`provided in my CV, I met the qualifications of a skilled artisan for purposes of
`
`the claims of the ’462 patent regardless of which party’s definition is adopted.
`
`36. Further, regardless of which party’s definition is adopted for a
`
`person of ordinary skill in the art, my opinions would not change.
`
`V. THE ’462 PATENT AND ITS ASSERTED CLAIMS
`37.
`I have read the ’462 patent, which is titled “Use of Long-Acting
`
`GLP-1 Peptides,” including its claims, and relevant portions of the file history
`
`of the ’462 patent.
`
`38.
`
`I have assumed that the earliest priority date to which the claims of
`
`the ’462 patent are entitled is July 1, 2012, which is the date recited on the face
`
`11
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`IPR2023-00724
`Page 00020
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`of the patent for foreign reference EP12174535, listed under “Foreign
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`Application Priority Data.” Therefore, I have been asked to assume that
`
`references pre-dating July 1, 2012, are prior art. To the extent Plaintiffs later
`
`assert and/or prove that the claims are entitled to an earlier priority or invention
`
`date, I reserve the right to supplement this report.
`
`A. The ’462 patent’s asserted claims
`39. The ’462 patent has one independent claim, which recites:
`
`1. A method for treating type 2 diabetes, comprising administering
`
`semaglutide once weekly in an amount of 1.0 mg to a subject in need
`
`thereof.
`
`40. Dependent claims 2, 3, 4, 5, 6, and 72 depend from claim 1, directly
`
`or indirectly, and are provided below.
`
`41. Dependent claim 2 recites:
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`2. The method according to claim 1, wherein the semaglutide is
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`administered by parenteral administration.
`
`
`2 I understand that Plaintiffs do not assert dependent claims 2 and 6 against the
`
`defendants. I recite claims 2 and 6 here, however, because I understand that they
`
`provide context for asserted claims 3 and 7, respectively.
`
`12
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`Novo Nordisk Exhibit 2537
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00021
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`

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`42. Dependent claim 3 recites:3
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`3. The method according to claim 2, wherein the solution is
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`administered by subcutaneous injection.
`
`43. Dependent claim 4 recites:
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`4. The method according to claim 1, wherein the semaglutide is
`
`administered in the form of an isotonic aqueous solution comprising
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`phosphate buffer at a pH in the range of 7.0-9.0.
`
`44. Dependent claim 5 recites:
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`5. The method according to claim 4, wherein the solution further
`
`comprises propylene glycol and phenol.
`
`45. Dependent claim 6 recites:
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`6. The method according to claim 4, wherein the pH is 7.4.
`
`46. Dependent claim 7 recites:
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`7. The method according to claim 6, wherein the solution further
`
`comprises propylene glycol and phenol.
`
`
`3 Claim 3 actually recites, “[t]he method according to claim 2 [which depends
`
`from claim 1], wherein the solution is administered by subcutaneous injection.”
`
`’462 patent at claim 3 (emphasis added). But neither claim 2 nor claim 1 recites
`
`“a solution.”
`
`13
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`Novo Nordisk Exhibit 2537
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00022
`
`

`

`
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`B. The Prosecution History of the ’462 Patent
`47. When the application for the ’462 patent was filed on July 21, 2017,
`
`independent claim 1 recited:
`
`1. A method for
`
`a) reduction of HbA1c;
`
`b) treatment of type 2 diabetes, hyperglycemia,
`impaired glucose tolerance, or non-insulin dependent
`diabetes; or
`
`c) treatment of obesity, reducing body weight and/or
`food intake, or inducing satiety;
`
`wherein said method comprises administration of a
`GLP-1 agonist to a subject in need thereof, wherein said
`GLP-1 agonist
`
`i) has a half-life of at least 72 hours;
`
`ii) is administered in an amount of at least 0.7 mg per
`week, such an amount equivalent to at least 0.7 mg
`semaglutide per week; and
`
`iii) is administered once weekly or less often.
`
`’462 File history at NN-OZEM-000003828 (patent specification as filed).4
`
`
`4 For a cited document that is a journal article, book chapter, or international
`
`patent application publication, or similar,