UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`SUN PHARMACEUTICAL INDUSTRIES LTD.
`and
`SUN PHARMACEUTICAL INDUSTRIES INC.,
`Petitioners,
`v.
`NOVO NORDISK A/S,
`Patent Owner.
`
`U.S. Patent No. 10,335,462 to Jensen
`Issue Date: July 2, 2019
`Title: Use of Long-Acting GLP-1 Peptides
`
`Inter Partes Review No. IPR2024-00107
`
`DECLARATION OF S. CRAIG DYAR, PH.D.,
`IN SUPPORT OF PETITION FOR
`INTER PARTES REVIEW OF U.S. PATENT NO. 10,335,462
`
`
`
`SUN EXHIBIT 1093, IPR2024-00107, PAGE 1
`
`

`

`
`
`TABLE OF CONTENTS
`
`Page
`I. QUALIFICATIONS AND BACKGROUND .......................................................................... 9
`A.
`EDUCATION AND EXPERIENCE ....................................................................................... 9
`B.
`PRIOR TESTIMONY ....................................................................................................... 15
`C.
`BASIS FOR OPINIONS AND MATERIALS CONSIDERED ................................................... 15
`D.
`RETENTION AND COMPENSATION ................................................................................ 15
`II. LEGAL STANDARDS .......................................................................................................... 15
`III. PERSON OF ORDINARY SKILL IN THE ART .................................................................. 18
`IV. BRIEF SUMMARY OF OPINIONS ...................................................................................... 19
`V. THE ’462 PATENT [EX. 1001] ............................................................................................. 21
`A.
`THE SPECIFICATION AND CLAIMS OF THE ’462 PATENT ............................................... 21
`B.
`THE PROSECUTION HISTORY OF THE ’462 PATENT ...................................................... 23
`VI. CLAIM CONSTRUCTION .................................................................................................... 25
`VII. BACKGROUND .................................................................................................................. 27
`A.
`PHARMACOKINETICS AND PHARMACODYNAMICS ........................................................ 27
`B.
`DRUG DEVELOPMENT - CLINICAL TRIAL DESIGN ........................................................ 30
`C.
`PHARMACOKINETICS AND PHARMACODYNAMICS RELATED TO GLP-1 AND
`SEMAGLUTIDE .............................................................................................................. 37
`1.
`GLP-1 .............................................................................................................. 37
`2.
`GLP-1 derivatives ........................................................................................... 38
`SEMAGLUTIDE CLINICAL TRIALS ................................................................................. 46
`D.
`VIII. SCOPE AND CONTENT OF THE PRIOR ART ................................................................ 50
`A. WO421 [EX. 1011] ..................................................................................................... 51
`B.
`LOVSHIN [EX. 1012].................................................................................................... 53
`C. WO537 [EX. 1015] ..................................................................................................... 55
`D.
`SEMAGLUTIDE CLINICAL TRIALS ................................................................................. 57
`1.
`NCT657 [Ex. 1013] ........................................................................................ 57
`2.
`NCT773 [Ex. 1014] ........................................................................................ 59
`3.
`Public Availability of ClinicalTrials.gov ........................................................ 61
`KNUDSEN 2004 [EX. 1032] .......................................................................................... 67
`LUND [EX. 1035] ......................................................................................................... 68
`
`E.
`F.
`
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`

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`
`
`SEINO [EX. 1038] ......................................................................................................... 72
`G.
`VICTOZA LABEL [EX. 1039] ......................................................................................... 73
`H.
`SHARGEL [EX. 1045] ................................................................................................... 76
`I.
`TAMIMI [EX. 1047] ...................................................................................................... 77
`J.
`FDA EXPOSURE RESPONSE 2003 [EX. 1048] ............................................................... 79
`K.
`ICH 1994 [EX. 1049] ................................................................................................... 81
`L.
`KNUDSEN 2010B [EX. 1066] ........................................................................................ 84
`M.
`ADDITIONAL PRIOR ART AND REFERENCES ................................................................... 84
`N.
`IX. UNPATENTABILITY OF THE ’462 PATENT .................................................................... 85
`A.
`GROUND 1: WO421 ANTICIPATED CLAIMS 1-3 OF THE ’462 PATENT .......................... 85
`1.
`Teachings of WO421 ...................................................................................... 85
`2.
`WO421 anticipated claim 1 ............................................................................ 85
`3.
`WO421 anticipated claim 2 ............................................................................ 90
`4.
`WO421 anticipated claim 3 ............................................................................ 91
`GROUND 2: LOVSHIN ANTICIPATED CLAIMS 1-3 OF THE ’462 PATENT ........................ 91
`1.
`Teachings of Lovshin ...................................................................................... 91
`2.
`Lovshin anticipated claim 1 ............................................................................ 91
`3.
`Lovshin anticipated claim 2 ............................................................................ 95
`4.
`Lovshin anticipated claim 3 ............................................................................ 95
`GROUND 3: CLAIMS 1-10 OF THE ’462 PATENT WOULD HAVE BEEN OBVIOUS OVER
`WO421 ........................................................................................................................ 96
`1.
`Claim 1 would have been obvious over WO ’421 .......................................... 96
`2.
`Claim 2 would have been obvious over WO ’421 ........................................ 104
`3.
`Claim 3 would have been obvious over WO ’421 ........................................ 105
`4.
`Claims 4-10 would have been obvious over WO ’421 considering the ’424
`publication..................................................................................................... 105
`GROUND 4: CLAIMS 1-10 OF THE ’462 PATENT WOULD HAVE BEEN OBVIOUS OVER
`WO537 CONSIDERING LOVSHIN ................................................................................ 106
`1.
`Claim 1 would have been obvious over WO537 considering Lovshin ........ 106
`2.
`Claim 2 would have been obvious over WO537 considering Lovshin ........ 115
`3.
`Claim 3 would have been obvious over WO537 considering Lovshin ........ 115
`4.
`Claims 4-10 would have been obvious over WO537 considering Lovshin .. 116
`GROUND 5: CLAIMS 1-10 OF THE ’462 PATENT WOULD HAVE BEEN OBVIOUS OVER
`NCT657 AND NCT773 .............................................................................................. 116
`
`D.
`
`B.
`
`C.
`
`E.
`
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`

`

`
`
`F.
`
`1.
`2.
`3.
`4.
`
`Claim 1 would have been obvious over NCT657 and NCT773 ................... 117
`Claim 2 would have been obvious over NCT657 and NCT773 ................... 124
`Claim 3 would have been obvious over NCT657 and NCT773 ................... 125
`Claims 4-10 would have been obvious over NCT657, NCT773, and the ’424
`publication..................................................................................................... 126
`NO SECONDARY CONSIDERATIONS OVERCOME PRIMA FACIE OBVIOUSNESS OF THE
`CLAIMED ALLEGED INVENTIONS ............................................................................... 126
`1.
`No unexpected results ................................................................................... 126
`2.
`No long-felt, unmet need or skepticism ........................................................ 127
`X. CONCLUSION ..................................................................................................................... 127
`
`
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`

`

`Table of Abbreviations
`
`
`Full Name of Cited Reference
`U.S. Patent App. Pub. No. 2011/0166321
`U.S. Patent App. Pub. No. US2007/0010424
`U.S. Patent No. 10,335,462
`U.S. Patent App. Pub. No. 2004/0102486
`U.S. Patent No. 5,512,549
`Bell, Hamster Preproglucagon Contains the Sequence of
`Glucagon and Two Related Peptides, 302 NATURE 716
`(1983)
`Blonde, Comparison of Liraglutide Versus Other Incretin-
`Related Anti-Hyperglycaemic Agents, 14
`(suppl. 2)
`DIABETES, OBESITY & METABOLISM 20 (2012)
`Drab, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus: Current Status and Future Prospects, 30
`PHARMACOTHERAPY 609 (2010)
`FDA Guidance
`for
`Industry, Exposure-Response
`Relationships - Study Design, Data, Analysis, and
`Regulatory Applications (Apr. 2003)
`Garber, Efficacy of Metformin in Type II Diabetes: Results
`of a Double-Blind, Placebo-Controlled, Dose-Response
`Trial, 102 AM. J. MED. 491 (1997)
`Holst, Truncated Glucagon-like Peptide I, an Insulin-
`Releasing Hormone from the Distal Gut, 211 (2) FEBS
`LETTERS 169 (1987)
`International Conference on Harmonisation; Dose-
`Response Information to Support Drug Registration;
`Guideline; Availability, 59 Fed. Reg. 55972 (Nov. 9, 1994)
`Kirillova, Results
`and Outcome Reporting
`in
`ClinicalTrials.gov, What Makes it Happen?, 7(6) PLOS
`ONE 1 (2012)
`
`Abbreviation
`’321 publication
`’424 publication
`’462 patent
`’486 publication
`’549 patent
`Bell
`
`Blonde
`
`Drab
`
`FDA Exposure Response
`2003
`
`Garber
`
`Holst
`
`ICH 1994
`
`Kirillova
`
`
`
`
`
`SUN EXHIBIT 1093, IPR2024-00107, PAGE 5
`
`

`

`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`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: The Therapeutic Promise from
`Animal Models, 64(suppl 167) INT J CLIN PRACT 4 (2010)
`Landersdorfer,
`Pharmacokinetic/Pharmacodynamic
`in Diabetes Mellitus,
`47(7) CLIN
`Modelling
`PHARMACOKINET 417 (2008)
`Landersdorfer,
`Population
`Mechanism-Based
`Pharmacokinetic Modelling in Diabetes: Vildagliptin as a
`Tight Binding Inhibitor and Substrate of Dipeptidyl
`Peptidase IV, 73 BR J CLIN PHARMACOL 391 (2011)
`Landersdorfer, Mechanism-Based Population Modelling of
`the Effects of Vildagliptin on GLP-1, Glucose and Insulin in
`Patients with Type 2 Diabetes, 73 BR J CLIN PHARMACOL
`373 (2011)
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus, 5 NATURE REVIEWS ENDOCRINOLOGY 262 (2009)
`Lund, Emerging GLP-1Receptor Agonists, 16 EXPERT
`OPINION 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)
`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)
`Møller, Mechanism-Based Population Modelling
`for
`Assessment of L-Cell Function Based on Total GLP-1
`Response Following an Oral Glucose Tolerance Test, 38 J.
`PHARMACOKINET PHARMACODYN 713 (2011)
`
`Abbreviation
`Knudsen 2004
`
`Knudsen 2010b
`
`Landersdorfer 2008
`
`Landersdorfer 2011a
`
`Landersdorfer 2011b
`
`Lovshin
`
`Lund
`
`Madsbad
`
`Mojsov
`
`Moller
`
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`
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`

`

`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Monami, Effects of Glucagon-Like Peptide-1 Receptor
`Agonists on Body Weight: A Meta-Analysis, 2012
`EXPERIMENTAL DIABETES RSCH. 1 (2012)
`Murphy, Review of the Safety and Efficacy of Exenatide
`Once Weekly for the Treatment of Type 2 Diabetes Mellitus,
`46 ANN PHARMACOTHER 812 (2012)
`Clinical Trial No. NCT00696657
`Clinical Trial No. NCT00851773
`Rohatagi, Model-Based Development of a PPARγ Agonist,
`Rivoglitazone, to Aid Dose Selection and Optimize Clinical
`Trial Designs, 48 J. CLIN. PHARM. 1420 (2008)
`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)
`Shargel,
`APPLIED
`BIOPHARMACEUTICS
`PHARMACOKINETICS (5th ed. 2005)
`Tamimi, Drug Development: From Concept to Marketing!,
`113 NEPHRON CLIN PRACT 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. 2010)
`International Patent App. Pub. No. WO 2011/058193
`International Patent App. Pub. No. WO 2011/073328
`International Patent App. Pub. No. WO 2011/138421
`International Patent App. Pub. No. WO 91/11457
`International Patent App. Pub. No. WO 2006/097537
`
`&
`
`Abbreviation
`Monami
`
`Murphy
`
`NCT657
`NCT773
`Rohatagi
`
`Seino
`
`Shargel
`
`Tamimi
`
`Tasneem
`
`Victoza label
`WO193
`WO328
`WO421
`WO457
`WO537
`
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`
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`

`

`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Yun, Pharmacokinetic and Pharmacodynamic Modelling of
`the Effects of Glimepiride on Insulin Secretion and Glucose
`Lowering in Healthy Humans, 31 J. CLIN. PHARM. & THER.
`469 (2006)
`Zarin, The ClinicalTrials.gov Results Database—Update
`and Key Issues, 364 NEW ENGL. J. MED. 852 (2011)
`
`Abbreviation
`Yun
`
`Zarin
`
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`
`
` My name is S. Craig Dyar, Ph.D. I have been retained by counsel for
`
`Petitioners Sun Pharmaceutical Industries Ltd. and Sun Pharmaceutical Industries
`
`Inc. (collectively “Sun”). I understand that Sun is submitting a petition for inter
`
`partes review (“IPR”) of U.S. Patent No. 10,335,462 (“’462 patent,” attached as Ex.
`
`1001), which is assigned to Novo Nordisk A/S. It is my understanding that Sun is
`
`requesting that the United States Patent and Trademark Office (“USPTO”) cancel
`
`all claims of the ’462 patent as unpatentable. I also understand that Mylan has filed
`
`and succeeded in instituting an IPR with respect to the ’462 patent in IPR2023-00724
`
`(the “Mylan IPR”). In support of the Mylan IPR, William J. Jusko, Ph.D. submitted
`
`a declaration (Ex. 1005). I have reviewed Dr. Jusko’s declaration and agree with it.
`
`Therefore, I have adopted it and, accordingly, submit this expert declaration in
`
`support of Sun’s IPR petition for the ’462 patent.
`
`I.
`
`QUALIFICATIONS AND BACKGROUND
`A. EDUCATION AND EXPERIENCE
`
`I hold a Bachelor’s degree in Biology from the University of South
`
`Carolina, a Bachelor’s degree in Pharmacy from the Medical University of South
`
`Carolina, Charleston, and a Ph.D. in Pharmaceutical Science from the Medical
`
`University of South Carolina, Charleston.
`
`
`
`I have almost 40 years of experience in the pharmaceutical sciences,
`
`including pharmacy, industry, and research.
`
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`
`
`
`I am the President of SCD Pharma Consulting. My specialty and
`
`research focus broadly include sterile formulations with specific expertise in the
`
`development of injectable and emulsion formulations with extensive experience
`
`with the commercial manufacture of pharmaceutical products including their
`
`pharmacokinetic development.
`
`
`
`Concurrently to my position at SCD Pharma Consulting, I was an
`
`Assistant Professor in the School of Pharmacy at South University. Prior to my
`
`position at South University, I have held numerous positions at Pfizer, with my most
`
`recent positions being Associate Director and Team Leader.
`
`
`
`In my capacity as a pharmaceutical consultant, I have provided advice
`
`on drug development from discovery to post-launch, life-cycle planning, project
`
`management, compound licensing and business development with a focus on drug
`
`delivery technologies including transdermal formulations (including patches),
`
`immediate and sustained release oral tablets, topical solutions, creams and ointments
`
`(dermal and ophthalmic), sublingual tablets, suppositories, targeted delivery systems
`
`(dendrimer and others), orally dissolving tablets, and injectables among others.
`
`
`
`As an assistant professor, I taught graduate courses in pharmacy. The
`
`course material involved a variety of topics including injection delivery
`
`pharmacokinetics, drug solubility for solutions and formulation development. The
`
`pharmacokinetics courses provided the student with an understanding of conceptual
`
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`
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`and mathematical treatment of Absorption, Distribution, Metabolism and Excretion
`
`processes (ADME) including the ability to apply this knowledge clinically to support
`
`the safe and effective management of individual patients. As an assistant professor,
`
`I included topics such as design of drug dosage regimens, therapeutic drug
`
`monitoring and adjustment of drug therapy. The application of these principles was
`
`illustrated and reinforced through discussion of pertinent drugs and case examples
`
`in a small team learning environment. The pharmaceutics courses covered a
`
`historical perspective of the evolution of modern dosage forms, governing laws,
`
`fundamentals of physical pharmacy, pharmacokinetic principles, and topics
`
`pertinent to the design, production, and stability of drugs and dosage forms.
`
`
`
`The course lectures included the study and application of physical-
`
`chemical principles and quantitative skills necessary for the design, formulation, and
`
`effective use of dosage forms to assure product performance and achieve the desired
`
`therapeutic outcomes. Lectures also focused on the rationale for design, intended
`
`performance characteristics, and the proper use of dosage forms to optimize clinical
`
`outcomes. The course laboratory complemented, and augmented topics covered in
`
`pharmaceutics lectures. Students worked in small groups to solve or elucidate
`
`assigned problems or theories. Students utilized reading material and other resources
`
`to perform and evaluate in vitro experiments (including computer simulations). Also,
`
`I directed graduate students in the laboratory to develop novel drug delivery systems.
`
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`
`
`
`
`As an Associate Director and Team Leader at Pfizer, I led
`
`Pharmaceutical Sciences Teams on ophthalmology and dermatology projects by
`
`serving as the single point of accountability and technical expert for projects from
`
`Preclinical to Phase III stages of development. I was responsible for managing the
`
`timelines and
`
`resources
`
`including a multimillion-dollar budget.
`
`I
`
`led
`
`multidisciplinary global teams composed of 8-12 colleagues in analytical,
`
`formulation, regulatory, quality assurance and supply chain areas in the resolution
`
`of several manufacturing issues and developed guidelines to improve manufacture
`
`practices. I also had responsibilities at Pfizer for drug delivery technology
`
`development where I utilized several solubilization enhancement techniques such as
`
`hot melt extrusion, super critical fluids, lipids, and cyclodextrins among others. I
`
`also used polyvinylpyrrolidone (i.e., PVP) as a solubility enhancer for APIs in
`
`transdermal systems well before the priority date of the patents-in-suit and continue
`
`to do so today. The use of PVP as a solubilizer in transdermal systems and other
`
`pharmaceutical delivery systems is common. For that matter, PVP’s solubilizer
`
`function is reported in the Handbook of Pharmaceutical Excipients.
`
` For 8 years at Pfizer, I was also responsible for external drug delivery
`
`technology evaluation available from any company in the world. During this time, I
`
`interacted with numerous drug delivery companies and managed several projects.
`
`The technologies included transdermal systems, sustained release oral and
`
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`
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`injectables, ocular implants/injections, sublingual, solubility enhancement methods,
`
`among others.
`
`
`
`16.
`
`I managed the COX-2 franchise for Worldwide Pharmaceutical
`
`Science by serving as the pharmaceutical science member of the COX-2 life-cycle
`
`team composed of members from marketing, regulatory, clinical pharmacokinetics,
`
`medical, and legal. My specific responsibilities included the following: I chaired
`
`celecoxib reformulation team composed of members from the previously listed
`
`groups. I developed a proposal and obtained endorsement of the same for
`
`multimillion-dollar proof of concept studies leading to a program in late-stage
`
`development. I defined the pharmaceutical science strategy for COX-2 programs and
`
`obtained endorsement from senior leaders in marketing, regulatory, clinical
`
`pharmacokinetics, medical, and legal, then provided guidance to pharmaceutical
`
`science COX-2 teams regarding this strategy. I also pioneered an endorsed idea,
`
`which used an alternate formulation approach reducing cost ($8 M) and time (two
`
`years), required to reach the market. Additionally, I chaired two cross-functional
`
`product enhancement management teams. As part of these responsibilities, I
`
`interacted extensively with medical with regard to designing and interpreting clinical
`
`studies to assess pain relief, including the use of the Visual Analog Scale (VAS)
`
`among others.
`
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`
`
` Throughout my career, I have published several peer-reviewed articles
`
`related to pharmaceutical sciences, as well as a book chapter on Melt-Extruded
`
`Particulate Dispersions in Pharmaceutical Extrusion Technology. I have also been
`
`invited to give presentations at national meetings, including “How to Pursue and
`
`Assess Potential Technologies as Synergistic Fits for Your Program,” “Navigating
`
`the Challenges of Early Phase Development in Ophthalmology,” and “Technology
`
`Differentiation: How Are Similar Technologies Effectively Evaluated?”
`
`
`
`I am a member of Rho Chi Honor Society, which is an academic
`
`pharmacy honor society. I am also member of the American Association of
`
`Pharmaceutical Sciences. Additionally, I am a Fellow of the American Foundation
`
`for Pharmaceutical Education
`
`(AFPE)—an organization
`
`that
`
`supports
`
`pharmaceutical education and from which I received a fellowship during my
`
`graduate work.
`
`
`
`I am also a Senior Director and the Head of Quality at Roivant, Inc. in
`
`charge of managing quality assurance for subsidiaries developing novel Phase I and
`
`II medicines.
`
` A copy of my CV, Exhibit 1094, provides a more comprehensive
`
`review of my work and describes my qualifications in greater detail, including a list
`
`of all publications that I authored during my career.
`
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`SUN EXHIBIT 1093, IPR2024-00107, PAGE 14
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`

`

`
`
`B.
`
`
`
`PRIOR TESTIMONY
`In the past four years, I have testified in the following proceedings:
`
`• UCB, Inc., et al. v. Mylan Technologies, Inc., No. 2:19-cv-00128 (D. Vt.);
`• Abeona Therapeutics Inc. v. Regenxbio Inc., AAA No.: 01-20-0005-3750;
`
`• Merck, Sharp and Dohme et al. v Mylan Pharmaceuticals et al., No. 1:19-
`cv-00101 (N.D. W.Va.);
`
`• Bial - Portela & CA S.A., et al. v. Apotex Inc., et al., No. 1:18-cv-00382
`(D. Del.); and
`
`• Amphastar Pharmaceuticals, Inc., v. Aegis Therapeutics, LLC, IPR2021-
`01324.
`C. BASIS FOR OPINIONS AND MATERIALS CONSIDERED
` A list of the materials I considered, in addition to my experience,
`
`education, and training, to provide the opinions contained in this declaration is
`
`attached as Exhibit A.
`
`D. RETENTION AND COMPENSATION
`
`I have been retained by counsel for Sun as a technical expert to provide
`
`certain of my opinions regarding the ’462 patent. I receive $450 per hour for this
`
`work. No part of my compensation is dependent upon my opinions given or the
`
`outcome of this proceeding.
`
`II.
`
`LEGAL STANDARDS
`
`In preparing and forming my opinions set forth in this declaration, I
`
`have been informed by counsel of the relevant legal principles. I applied my
`
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`

`

`
`
`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 proceeding.
`
`
`
`I understand that my opinions regarding unpatentability are presented
`
`from the viewpoint of a person of ordinary skill in the art (“POSA” or “skilled
`
`artisan”) in the field of technology of the patent as of the patent’s priority date. In
`
`this declaration, my opinions are premised on the perspective of a POSA at the time
`
`of the earliest claimed priority date for the ’462 patent, which I have been informed
`
`for this proceeding is July 1, 2012.2 See Ex. 1001 (’462 patent) at 1.
`
`
`
`I have been informed that Sun bears the burden of proving
`
`unpatentability by a preponderance of the evidence. I am informed that this
`
`
`1 In performing my analysis and reaching my opinions and conclusions, I have been
`
`informed of and have been advised to apply various legal principles relating to
`
`unpatentability, which I set forth herein. In setting forth these legal standards, it is
`
`not my intention 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 conclusions I
`
`am providing.
`
`2 To the extent Patent Owner asserts that the claims of the ’462 patent are entitled to
`
`an earlier priority or invention date, I reserve the right to supplement this declaration.
`
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`“preponderance-of-the-evidence” standard means that the Patent Trial and Appeal
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`Board must find it more likely than not that the claims are unpatentable.
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`I understand that for a patent claim to be unpatentable as anticipated, a
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`prior art reference must disclose each element of the claim expressly and/or
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`inherently as arranged in the claim.
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` Counsel has informed me that the concept of patent obviousness
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`involves four factual inquiries: (1) the scope and content of the prior art; (2) the
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`differences between the claimed invention and the prior art; (3) the level of ordinary
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`skill in the art; and (4) secondary considerations of non-obviousness.
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`It is my understanding from counsel that when there is some recognized
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`reason to solve a problem, and there are a finite number of identified, predictable
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`and known solutions, a person of ordinary skill in the art has good reason to pursue
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`the known options within his or her technical grasp. If such an approach leads to the
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`expected success, it is likely not the product of innovation but of ordinary skill and
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`common sense. It is my understanding that any need or problem known in the field
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`of endeavor at the time of invention or addressed by the patent can provide a reason
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`for combining prior art elements to arrive at the claimed subject matter. I understand
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`that only a reasonable expectation of success is necessary to show obviousness.
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`- 17 -
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`SUN EXHIBIT 1093, IPR2024-00107, PAGE 17
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`III. PERSON OF ORDINARY SKILL IN THE ART
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`In my opinion, the following definition of a person of ordinary skill in
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`the art (“POSA” or “skilled artisan”) applies to the claims of the ’462 patent.
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` A POSA here would have had (1) an M.D., a Pharm. D., or a Ph.D. in
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`pharmacy, chemical engineering, bioengineering, chemistry, or related discipline;
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`(2) at least two years of experience in protein or peptide therapeutic development
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`and/or manufacturing or diabetes treatments; and (3) experience with the
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`development, design, manufacture, formulation, or administration of therapeutic
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`agents, and the literature concerning protein or peptide formulation and design, or
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`diabetes treatments.
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` Alternatively, the POSA would be (1) a highly skilled scientist lacking
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`an M.D., Pharm. D., or Ph.D., but would have (2) more than five years of experience
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`in the area of protein or peptide therapeutic development and/or manufacturing or
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`diabetes
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`treatments; and/or (3) experience with
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`the development, design,
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`manufacture, formulation, or administration of therapeutic agents, and the literature
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`concerning protein or peptide formulation and design, or diabetes treatments.
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` A POSA would have understood the prior art references referred to
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`herein and would have the capability to draw inferences. It is understood that, to the
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`extent necessary, a POSA may collaborate with one or more other POSAs for one or
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`more aspects with which the other POSA may have expertise, experience, and/or
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`- 18 -
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`SUN EXHIBIT 1093, IPR2024-00107, PAGE 18
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`knowledge. Additionally, a POSA could have had a lower level of formal education
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`than what I describe here if the person has a higher degree of experience.
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` As shown by my qualifications provided in my CV and as explained in
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`this declaration, I met the qualifications of a POSA for purposes of the ’462 patent.
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`I understand that Mylan’s formulation expert, Dr. Paul Dalby,
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`submitted a declaration with his opinions about why claims 4–10 of the ’462 patent,
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`directed to formulation-related elements, are obvious over the prior art in IPR2023-
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`00724 (the “Mylan IPR”). I defer to Dr. Dalby’s opinion on the formulation-related
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`elements of claims 4–10 of the ’462 patent.
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`IV. BRIEF SUMMARY OF OPINIONS
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`In my opinion, International Patent Application Publication No. WO
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`2011/138421 (“WO421”) anticipates claims 1–3 of the ’462 patent.
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`In my opinion, a review article titled “Incretin-Based Therapies for
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`Type 2 Diabetes Mellitus” (“Lovshin”) authored by Julie A. Lovshin and Daniel J.
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`Drucker, which was published in May 2009, anticipates claims 1–3 of the ’462
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`patent.
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`In my opinion, claims 1–10 of the ’462 patent would have been obvious
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`over WO421 considering U.S. Patent Application Publication No. 2007/0010424 A1
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`(“’424 Publication”). It is my understanding that Dr. Dalby offered an opinion that
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`- 19 -
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`SUN EXHIBIT 1093, IPR2024-00107, PAGE 19
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`claims 4–10 would have been obvious over WO421 considering the ’424
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`Publication, and I defer to his opinion for claims 4-10.
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`In my opinion, claims 1-10 of the ’462 patent would have been obvious
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`over International Patent Application Publication No. WO 2006/097537 A2
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`(“WO537”) considering Lovshin. It is my understanding that Dr. Dalby offered an
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`opinion that claims 4-10 would have been obvious over WO537 considering
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`Lovshin, and I defer to his opinion for claims 4-10.
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`
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`In my opinion, claims 1-10 of the ’462 patent would have been obvious
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`over Clinical Trial No. NCT00696657 (“NCT657”), Clinical Trial No.
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`NCT00851773 (“NCT773”), and the ’424 Publication. It is my understanding that
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`Dr. Dalby offered an opinion that claims 4-10 would have been obvious over
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`NCT657, NCT773, and the ’424 Publication, and I defer to his opinion for claims 4-
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`10.
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` Finally, there are no apparent secondary considerations supporting
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`nonobviousness of the claims. I reserve the right to address any secondary
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`considerations put forth by Patent Owner in any later response to this declaration or
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`the petition it accompanies.
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`- 20 -
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`SUN EXHIBIT 1093, IPR2024-00107, PAGE 20
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`V.
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`THE ’462 PATENT [EX. 1001]
`A. THE SPECIFICATION AND CLAIMS OF THE ’462 PATENT
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`I have read the ’462 patent, titled “Use of Long-Acting GLP-1
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`Peptides,” and reviewed the relevant portions of the prosecution history of the ’462
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`patent (Ex. 1002). The ’462 patent issued from U.S. Patent Application No.
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`15/656,042 (“’042 Application”), filed July 21, 2017, which is a continuation of U.S.
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`Application No. 14/409,493, filed as PCT/EP2013/063004, filed June 21, 2013, and
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`claims priority to Provisional Application No. 61/708,162, filed October 1, 2012,
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`and Provisional Application No. 61/694,837, filed August 30, 2012, and European
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`patent 12174535, filed July 1, 2012,