UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner,
`
`v.
`
`NOVO NORDISK A/S,
`
`Patent Owner.
`
`Case No. IPR2023-00724
`
`Patent No. 10,335,462
`
`DECLARATION OF JOHN BANTLE, M.D., IN SUPPORT OF PETITION
`FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 10,335,462
`
`MPI EXHIBIT 1003 PAGE 1
`
`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1003, p. 1 of 178
`
`

`

`TABLE OF CONTENTS
`
`
`Page
`
`
`I.
`
`Qualifications and Background ...................................................................... 9
`A.
`Education and Experience; Prior Testimony........................................ 9
`B.
`Basis for Opinions and Materials Considered .................................... 12
`C.
`Retention and Compensation ............................................................. 12
`Summary of Opinions ................................................................................... 12
`II.
`III. Legal Standards ............................................................................................ 14
`IV. Person of Ordinary Skill in the Art ............................................................... 16
`V.
`The ’462 Patent (Ex. 1001) and Its Claims .................................................. 17
`VI. Claim Construction ....................................................................................... 24
`VII. Background on Diabetes and the use of GLP-1 Derivatives for the
`Treatment of Diabetes................................................................................... 26
`A. Diabetes Generally ............................................................................. 26
`B. Diabetes Treatment............................................................................. 28
`C.
`The Use of GLP-1 Derivatives to Treat Diabetes .............................. 30
`D. Use of Liraglutide to Treat Diabetes .................................................. 32
`E.
`Extended-Use GLP-1 Receptor Agonists ........................................... 36
`VIII. Scope and Content of the Prior Art .............................................................. 46
`A.
`Lovshin (Ex. 1012) ............................................................................. 47
`B. U.S. Patent Application Pub. No. US2007/0010424 (Ex. 1016) ....... 49
`C. WO 2006/097537 (Ex. 1015) ............................................................. 53
`D. WO 2011/138421 (Ex. 1011) ............................................................. 59
`E.
`Semaglutide Clinical Trial Records ................................................... 63
`1.
`Clinical Trial No. NCT00696657 (Ex. 1013) .......................... 63
`2.
`Clinical Trial No. NCT00851773 (Ex. 1014) .......................... 65
`3.
`ClinicalTrials.gov is a Part of the POSA’s Knowledge ........... 67
`Other Art that Informs the POSA’s Knowledge ................................ 75
`1.
`Drucker 2003 (Ex. 1023) ......................................................... 75
`
`F.
`
`2
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`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`Holst 2004 (Ex. 1028) .............................................................. 76
`2.
`Knudsen 2001 (Ex. 1031) ........................................................ 80
`3.
`Knudsen 2004 (Ex. 1032) ........................................................ 84
`4.
`Knudsen patent (U.S. Patent No. 6,268,343) (Ex. 1034) ........ 89
`5.
`Lund (Ex. 1035) ....................................................................... 94
`6.
`Victoza label (Ex. 1039) .......................................................... 94
`7.
`8. WO 03/002136 (Ex. 1041) ....................................................... 98
`9.
`Additional prior art and references ........................................ 103
`IX. Unpatentability of the Claims of the ’462 Patent ....................................... 103
`A. Ground 1: WO421 Anticipated Claims 1–3 ..................................... 103
`1. WO421 anticipated independent claim 1 ............................... 103
`2. WO421 anticipated claim 2 ................................................... 116
`3. WO421 anticipated claim 3 ................................................... 118
`B. Ground 2: Lovshin Anticipated Claims 1-3 ..................................... 119
`1.
`Lovshin anticipated independent claim 1 .............................. 120
`2.
`Lovshin anticipated claim 2 ................................................... 126
`3.
`Lovshin anticipated claim 3 ................................................... 127
`C. Ground 3: Claims 1–10 of the ’462 patent would have been
`obvious over WO421 alone or in view of the ’424 publication ....... 128
`1.
`Claim 1 of the ’462 patent would have been obvious over
`WO421 alone ......................................................................... 128
`Claims 2 and 3 of the ’462 patent would have been
`obvious over WO421 alone ................................................... 135
`Claims 4–10 of the ’462 patent would have been obvious
`over WO421 in view of the ’424 publication ........................ 139
`D. Ground 4: Claims 1–10 of the ’462 patent would have been
`obvious over WO537 in view of Lovshin ........................................ 139
`
`2.
`
`3.
`
`3
`
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`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`X.
`
`E.
`
`F.
`
`1.
`
`2.
`
`3.
`
`2.
`
`3.
`
`Claim 1 of the ’462 patent would have been obvious over
`WO537 in view of Lovshin .................................................... 139
`Claims 2 and 3 of the ’462 patent would have been
`obvious over WO537 in view of Lovshin .............................. 148
`Claims 4–10 of the ’462 patent would have been obvious
`over WO537 in view of Lovshin ........................................... 150
`Ground 5: Claims 1–10 of the ’462 patent would have been
`obvious over NCT657 in view of NCT773 and further in view
`of the ’424 publication ..................................................................... 150
`1.
`Claim 1 of the ’462 patent would have been obvious over
`NCT657 in view of NCT773 ................................................. 151
`Claims 2 and 3 of the ’462 patent would have been
`obvious over NCT657 in view of NCT773 ........................... 167
`Claims 4–10 of the ’462 patent would have been obvious
`over NCT657 in view of NCT773 and further in view of
`the ’424 publication ............................................................... 170
`No Secondary Considerations Overcome Prima Facie
`Obviousness ...................................................................................... 170
`1.
`No unexpected results ............................................................ 171
`2.
`A POSA would have known there was no long-felt,
`unmet need for a once weekly GLP-1 receptor agonist or
`1.0 mg dosing, nor was there any skepticism in the art ......... 171
`Reservation of Rights ................................................................................. 171
`
`4
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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
`
`U.S. Patent No. 10,335,462 file history excerpts
`
`U.S. Patent No. 5,512,549
`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)
`Highlights of Prescribing Information: Bydureon, Revised:
`01/2012
`Highlights of Prescribing Information: Byetta, Revised:
`10/2009
`ClinicalTrials.gov Background, CLINICALTRIALS.GOV,
`https://clinicaltrials.gov/ct2/about-site/background (last
`visited Mar. 10, 2023)
`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)
`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)
`
`5
`
`Abbreviation
`’321 publication
`’424 publication
`(Ex. 1016)
`’462 patent
`(Ex. 1001)
`’462 file history
`(Ex. 1002)
`’549 patent
`Banting
`
`Bell
`
`Bydureon label
`
`Byetta label
`
`ClinicalTrials.gov
`Background
`
`Drab
`
`Drucker 2003
`
`Drucker 2006
`
`Glaesner
`
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`

`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`HARRISON’S PRINCIPLES OF INTERNAL MED., Chapter 338
`(Fauci et al. eds. 17th ed. 2008)
`Award: ClinicalTrials.gov,
`https://ash.harvard.edu/news/clinicaltrials.gov (last visited
`Mar. 10, 2023)
`Holst, Truncated Glucagon-like Peptide I, an Insulin-
`Releasing Hormone from the Distal Gut, 211 (2) 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)
`Kirillova, Results and Outcome Reporting in
`ClinicalTrials.gov, What Makes it Happen?, 7(6) PLOS
`ONE 1 (2012)
`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)
`
`Abbreviation
`Harrison’s
`
`Harvard Award
`
`Holst 1987
`
`Holst 2004
`
`Jimenez-Solem
`
`Kim
`
`Kirillova
`
`Knudsen 2001
`
`Knudsen 2004
`
`Knudsen 2010
`
`6
`
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`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`U.S. Patent No. 6,268,343
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus, 5 NATURE REV. ENDOCRINOLOGY 262 (2009)
`Lund, Emerging GLP-1 Receptor Agonists, 16 EXPERT OP.
`ON EMERGING DRUGS 607 (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)
`NCT00167115, CLINICALTRIALS.GOV,
`https://www.clinicaltrials.gov/ct2/show/NCT00167115
`(last visited Mar. 10, 2023)
`NCT01933490, CLINICALTRIALS.GOV,
`https://www.clinicaltrials.gov/ct2/show/NCT01933490
`(last visited Mar. 10, 2023)
`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)
`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)
`
`Abbreviation
`Knudsen patent
`Lovshin
`(Ex. 1012)
`Lund
`
`Mojsov
`
`Monami
`
`NCT115
`
`NCT490
`
`NCT657
`(Ex. 1013)
`NCT773
`(Ex. 1014)
`Nielsen
`
`Seino
`
`7
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`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Abbreviation
`Tamimi
`
`Tasneem
`
`Full Name of Cited Reference
`Tamimi, Drug Development: From Concept to Marketing!,
`113 NEPHRON CLINICAL PRAC. 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)
`Vilsbøll, Glucagon-Like Peptide-1 and Diabetes
`Treatment, 21 INTERNATIONAL DIABETES MONITOR 1
`(2009).
`International Patent Application Pub. No. WO 03/002136 WO136
`International Patent Application Pub. No. WO
`WO328
`2011/073328
`International Patent Application Pub. No. WO
`2011/138421
`International Patent Application Publication No. WO
`91/11457
`International Patent Application Pub. No. WO
`2006/097537
`Zarin, The ClinicalTrials.gov Results Database—Update
`and Key Issues, 364 NEW ENGL. J. MED. 852 (2011)
`
`Victoza label
`Vilsbøll
`
`WO421
`(Ex. 1011)
`WO457
`
`WO537
`(Ex. 1015)
`Zarin
`
`8
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`
`1. My name is John P. Bantle, M.D. I have been retained by Mylan
`
`Pharmaceuticals Inc. (“Mylan”) to provide my expert opinions regarding the
`
`unpatentability of the claims of U.S. Patent No. 10,335,462 (“’462 patent”) (Ex.
`
`1001). I understand that Mylan intends to petition for inter partes review (“IPR”) of
`
`the ’462 patent, which is assigned to Novo Nordisk A/S. I also understand that, in
`
`the IPR petition, Mylan will request that the United States Patent and Trademark
`
`Office cancel all claims of the ’462 patent as unpatentable. I submit this expert
`
`declaration to address and support Mylan’s IPR petition for the ’462 patent.
`
`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 Dunedin, New Zealand, in
`
`9
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`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 patients with
`
`diabetes, including developing nutritional recommendations for people with diabetes
`
`and developing the national standards of care for diabetes patients.
`
`10
`
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`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.);
`
` BTG Int’l, Ltd. v Amneal Pharms. LLC, Amerigen Pharms., Inc., Teva
`Pharms. USA, Inc., Nos. 15-cv-5909, 16-cv-2449 and 17-cv-6435
`(D.N.J.);
`
` 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
`
` Novo Nordisk Inc. v. Mylan Institutional LLC,
`No. 19-cv-01551 (D. Del.).
`
`9. My qualifications are further described on my curriculum vitae,
`
`attached as Exhibit 1004.
`
`11
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`B.
`
`Basis for Opinions and Materials Considered
`
`10. Exhibit 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.
`
`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 $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 declaration, 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 obvious over the following combinations of
`
`references:
`
`a) Ground 1: WO421 anticipated claims 1-3 of the ’462 patent;
`
`b) Ground 2: Lovshin anticipated claims 1-3 of the ’462 patent;
`
`c) Ground 3: Claims 1–10 of the ’462 patent would have been obvious
`
`over WO421 in view of the ’424 publication;
`
`12
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`d) Ground 4: Claims 1–10 of the ’462 patent would have been obvious
`
`over WO537 in view of Lovshin; and
`
`e) Ground 5: Claims 1–10 of the ’462 patent would have been obvious
`
`over NCT657 in view of NCT773 and further in view of the ’424
`
`publication.
`
`14. As detailed below, WO421 disclosed all the limitations recited in
`
`claims 1–3 of the ’462 patent.
`
`15. However, to the extent the Board disagrees and finds that WO421 did
`
`not anticipate claims 1–3 of the ’462 patent, then, in light of the state of the art,
`
`WO421 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
`
`in doing so, rendering obvious claims 1–10 of the ’462 patent, alone or in view of
`
`the ’424 publication.
`
`16. Additionally, both WO537 in view of Lovshin, and NCT657 in view of
`
`NCT773 and further in view of the ’424 publication 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 in doing so, in both cases
`
`rendering obvious claims 1–10 of the ’462 patent.
`
`17.
`
`I understand that Mylan’s expert Dr. Paul Dalby is offering the opinion
`
`that it would have been obvious to a POSA to formulate semaglutide into an isotonic
`
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`aqueous solution having the various characteristics recited as limitations in
`
`dependent claims 4–10 of the ’462 patent.
`
`18.
`
`I understand that Patent Owner may present expert opinions regarding
`
`“secondary considerations” of non-obviousness of the method of treatment claims,
`
`and/or of other claims, in response to my declaration, and that I may be asked to
`
`address such opinions in the future. I therefore expressly reserve the right to address
`
`later all issues of secondary considerations that Patent Owner’s experts may raise.
`
`III. LEGAL STANDARDS
`
`19. To prepare and form my opinions set forth in this declaration, 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.
`
`
`1 As support for my analysis and to help me reach my opinions and conclusions, I
`
`was informed of and advised to apply various legal principles relating to
`
`unpatentability, which I set forth here. By setting forth these legal standards, 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 conclusions I provide.
`
`14
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`20.
`
`I have been informed that Mylan bears the burden of proving
`
`unpatentability by a preponderance of the evidence. I have been told that this means
`
`the PTAB must find it more likely than not that the claims are unpatentable.
`
`21.
`
`I understand that my opinions regarding unpatentability are presented
`
`from the viewpoint of a person of ordinary skill in the art (“POSA”) in the field of
`
`technology of the patent as of the patent’s priority date.
`
`22.
`
`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.
`
`23.
`
`I am told that the concept of patent obviousness involves four factual
`
`inquiries: (1) the scope and content of the prior art; (2) the differences between the
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`claimed invention and the prior art; (3) the level of ordinary skill in the art; and (4)
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`secondary considerations of non-obviousness.
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`24.
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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
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`options within his or her technical grasp. If such an approach leads to the expected
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`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 field of endeavor at the
`
`time of invention or addressed by the patent can provide a reason for combining
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`15
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`MPI EXHIBIT 1003 PAGE 15
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1003, p. 15 of 178
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`prior art elements to arrive at the claimed subject matter. I understand that only a
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`reasonable expectation of success is necessary to show obviousness.
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`IV. PERSON OF ORDINARY SKILL IN THE ART
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`25.
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`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
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`supplement my opinions on unpatentability if the Board adopts, or the parties agree
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`to, a different definition of a skilled artisan.
`
`26. The subject matter of claims 1–10 of the ’462 patent falls within the
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`medicinal chemical arts. A skilled artisan would have had (1) an M.D., a Pharm.D.,
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`or a Ph.D. in pharmacy, chemical engineering, bioengineering, chemistry, or related
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`discipline; (2) at least two years of experience in protein or peptide therapeutic
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`development and/or manufacturing or diabetes treatments; and (3) experience with
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`the 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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`27. Alternatively, the skilled artisan would be (1) a highly skilled scientist
`
`lacking an M.D., a Pharm.D., or a Ph.D., but would have (2) more than five years of
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`experience in the area of protein or peptide therapeutic development and/or
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`manufacturing or diabetes treatments; and/or (3) experience with the development,
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`design, manufacture, formulation, or administration of therapeutic agents, and the
`
`16
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
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`literature concerning protein or peptide formulation and design, or diabetes
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`treatments.
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`28. A skilled artisan would have understood the prior art references referred
`
`to herein and would have the capability to draw inferences. It is understood that, to
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`the extent necessary, a skilled artisan may collaborate with one or more other skilled
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`artisans for one or more aspects with which the other skilled artisan may have
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`expertise, experience, and/or knowledge. Additionally, a skilled artisan could have
`
`had a lower level of formal education than what I describe here if the person has a
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`higher degree of experience.
`
`29. As explained in this declaration and exemplified by the information
`
`provided in my CV, I met the qualifications of a skilled artisan for purposes of the
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`claims of the ’462 patent.
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`V. THE ’462 PATENT (EX. 1001) AND ITS CLAIMS
`
`30.
`
`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 (Ex. 1002).
`
`31.
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`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 of the
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`patent for foreign reference EP12174535, listed under “Foreign Application Priority
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`Data.” Therefore, I have been asked to assume that references pre-dating July 1,
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`17
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1003, p. 17 of 178
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`2012, are prior art. To the extent Patent Owner later asserts and/or proves that the
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`claims are entitled to an earlier priority or invention date, I reserve the right to
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`supplement this declaration.
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`A. The ’462 patent’s claims
`
`32. 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
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`1.0 mg to a subject in need thereof.
`
`33. Dependent claims 2–10 depend from claim 1, directly or indirectly, and
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`are provided below.
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`34. Dependent claim 2 recites:
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`2. The method according to claim 1, wherein the
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`semaglutide is administered by parenteral administration.
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`35. Dependent claim 3 recites:
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`3. The method according to claim 2, wherein the solution
`
`is administered by subcutaneous injection.
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`36. Dependent claim 4 recites:
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`4. The method according to claim 1, wherein the
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`semaglutide is administered in the form of an isotonic
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`aqueous solution comprising phosphate buffer at a pH in
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`the range of 7.0-9.0.
`
`37. Dependent claim 5 recites:
`
`18
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
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`5. The method according to claim 4, wherein the solution
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`further comprises propylene glycol and phenol.
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`38. Dependent claim 6 recites:
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`6. The method according to claim 4, wherein the pH is 7.4.
`
`39. Dependent claim 7 recites:
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`7. The method according to claim 6, wherein the solution
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`further comprises propylene glycol and phenol.
`
`40. Dependent claim 8 recites:
`
`8. The method according to claim 4, wherein the
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`phosphate buffer is a sodium dihydrogen phosphate
`
`buffer.
`
`41. Dependent claim 9 recites:
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`9. The method according to claim 1, wherein the
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`semaglutide is administered by subcutaneous injection in
`
`the form of an isotonic aqueous solution comprising at a
`
`sodium dihydrogen phosphate buffer at a pH in the range
`
`of 7.0-9.0, and wherein the solution further comprises
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`propylene glycol and phenol.
`
`42. Dependent claim 10 recites:
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`10. The method according to claim 9, wherein the pH is
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`7.4.
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`19
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
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`B.
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`The Prosecution History of the ’462 Patent
`
`43. 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.
`
`Ex. 1002 (File history) at 8.2
`
`
`2 For all cited documents that are not an issued U.S. patent or published U.S. patent
`
`application publication, the cited page number refers to the branded page number of
`
`the exhibit and not, for example, to the internal page numbering of a journal article,
`
`book chapter, or international patent application publication.
`
`
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`20
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
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`44. The Examiner rejected the filed claims on July 23, 2018, for
`
`indefiniteness of claim language, anticipation in view of the prior art, and double
`
`patenting over U.S. Patent No. 9,764,003. Id. at 307-18. On the merits of the
`
`anticipation rejections, the Examiner asserted that NCT00696657, which disclosed
`
`the use of semaglutide and liraglutide, Madsbad, which disclosed the use of several
`
`GLP-1 agonists, and Kim, which disclosed the use of exenatide, anticipated the
`
`claims because they each disclosed a method of treatment with at least 0.8 mg of
`
`GLP-1 agonist once weekly (NCT657 with 0.8 mg semaglutide; Madsbad with 4,
`
`15, and 30 mg albiglutide; and Kim with 0.8 and 2.0 mg exenatide), with all the other
`
`requirements satisfied (treating type 2 diabetes and reducing HbA1c, with a half-life
`
`in the required range, etc.). See Ex. 1002 (File history) at 312-15 (July 23, 2018
`
`Office Action).
`
`45. After these rejections, the applicants amended claim 1 to recite simply:
`
`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.
`
`See Ex. 1002 (File history) at 332.
`
`46. Showing the relevant edits in full redline makes clear the extent of the
`
`applicants’ changes:
`
`1. (Currently Amended) 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
`
`21
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1003, p. 21 of 178
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`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.
`
`E