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.
`
`
`
`
`
`Case No. IPR2024-00107
`Patent No. 10,335,462
`
`
`
`DECLARATION OF MELISSA E. WEINBERG, M.D.,
`IN SUPPORT OF PETITION
`FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 10,335,462
`
`
`
`
`
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 1
`
`

`

`TABLE OF CONTENTS
`
`Page
`QUALIFICATIONS AND BACKGROUND .................................................................. 9
`
`I.
`
`A.
`
`B.
`
`C.
`
`D.
`
`Education and Experience; Prior Testimony .......................................................... 9
`
`Prior Testimony .................................................................................................... 10
`
`Basis for Opinions and Materials Considered ...................................................... 10
`
`Retention and Compensation ................................................................................ 11
`
`II.
`
`SUMMARY OF OPINIONS ........................................................................................... 11
`
`III. LEGAL STANDARDS .................................................................................................... 13
`
`IV. PERSON OF ORDINARY SKILL IN THE ART ........................................................ 14
`
`V.
`
`THE ’462 PATENT (EX. 1001) AND ITS CLAIMS .................................................... 16
`
`A.
`
`B.
`
`The ’462 patent’s claims ....................................................................................... 16
`
`The Prosecution History of the ’462 Patent .......................................................... 19
`
`VI. CLAIM CONSTRUCTION ............................................................................................ 24
`
`VII. BACKGROUND ON DIABETES AND THE USE OF GLP-1 DERIVATIVES
`FOR THE TREATMENT OF DIABETES .............................................................................. 26
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`Diabetes Generally ................................................................................................ 26
`
`Diabetes Treatment ............................................................................................... 27
`
`The Use of GLP-1 Derivatives to Treat Diabetes ................................................. 30
`
`Use of Liraglutide to Treat Diabetes ..................................................................... 32
`
`Extended-Use GLP-1 Receptor Agonists ............................................................. 36
`
`VIII. SCOPE AND CONTENT OF THE PRIOR ART ........................................................ 46
`
`A.
`
`B.
`
`Lovshin (Ex. 1012) ............................................................................................... 47
`
`U.S. Patent Application Pub. No. US2007/0010424 (Ex. 1016) .......................... 49
`
`C. WO 2006/097537 (Ex. 1015) ................................................................................ 54
`
`2
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 2
`
`

`

`D. WO 2011/138421 (Ex. 1011) ................................................................................ 61
`
`E.
`
`Semaglutide Clinical Trial Records ...................................................................... 65
`
`1.
`
`2.
`
`3.
`
`Clinical Trial No. NCT00696657 (Ex. 1013) ........................................... 65
`
`Clinical Trial No. NCT00851773 (Ex. 1014) ........................................... 68
`
`ClinicalTrials.gov is a Part of the POSA’s Knowledge ............................ 70
`
`F.
`
`Other Art that Informs the POSA’s Knowledge ................................................... 78
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Drucker 2003 (Ex. 1023) .......................................................................... 78
`
`Holst 2004 (Ex. 1028) ............................................................................... 79
`
`Knudsen 2001 (Ex. 1031) ......................................................................... 83
`
`Knudsen 2004 (Ex. 1032) ......................................................................... 87
`
`Knudsen patent (U.S. Patent No. 6,268,343) (Ex. 1034) .......................... 93
`
`Lund (Ex. 1035) ........................................................................................ 98
`
`Victoza label (Ex. 1039) ........................................................................... 98
`
`WO 03/002136 (Ex. 1041) ...................................................................... 102
`
`Additional prior art and references ......................................................... 108
`
`IX. UNPATENTABILITY OF THE CLAIMS OF THE ’462 PATENT ........................ 108
`
`A.
`
`Ground 1: WO421 Anticipated Claims 1–3 ........................................................ 108
`
`1.
`
`2.
`
`3.
`
`WO421 anticipated independent claim 1 ................................................ 108
`
`WO421 anticipated claim 2 .................................................................... 121
`
`WO421 anticipated claim 3 .................................................................... 123
`
`B.
`
`Ground 2: Lovshin Anticipated Claims 1-3 ........................................................ 124
`
`1.
`
`2.
`
`3.
`
`Lovshin anticipated independent claim 1 ............................................... 125
`
`Lovshin anticipated claim 2 .................................................................... 131
`
`Lovshin anticipated claim 3 .................................................................... 132
`
`C.
`
`Ground 3: Claims 1–10 of the ’462 patent would have been obvious over
`WO421 alone or in view of the ’424 publication ............................................... 133
`
`3
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 3
`
`

`

`1.
`
`2.
`
`3.
`
`Claim 1 of the ’462 patent would have been obvious over WO421
`alone ........................................................................................................ 133
`
`Claims 2 and 3 of the ’462 patent would have been obvious over
`WO421 alone .......................................................................................... 140
`
`Claims 4–10 of the ’462 patent would have been obvious over
`WO421 in view of the ’424 publication ................................................. 144
`
`D.
`
`Ground 4: Claims 1–10 of the ’462 patent would have been obvious over
`WO537 in view of Lovshin................................................................................. 144
`
`1.
`
`2.
`
`3.
`
`Claim 1 of the ’462 patent would have been obvious over WO537
`in view of Lovshin .................................................................................. 144
`
`Claims 2 and 3 of the ’462 patent would have been obvious over
`WO537 in view of Lovshin..................................................................... 153
`
`Claims 4–10 of the ’462 patent would have been obvious over
`WO537 in view of Lovshin..................................................................... 155
`
`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 ......... 155
`
`1.
`
`2.
`
`3.
`
`Claim 1 of the ’462 patent would have been obvious over NCT657
`in view of NCT773 ................................................................................. 156
`
`Claims 2 and 3 of the ’462 patent would have been obvious over
`NCT657 in view of NCT773 .................................................................. 172
`
`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............................................................................................... 175
`
`F.
`
`No Secondary Considerations Overcome Prima Facie Obviousness ................. 175
`
`1.
`
`2.
`
`No unexpected results ............................................................................. 176
`
`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 ................................................................ 176
`
`RESERVATION OF RIGHTS ..................................................................................... 176
`
`X.
`
`
`4
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 4
`
`

`

`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)
`
`Abbreviation
`
`’321 publication
`
`’424 publication
`(Ex. 1016)
`
`’462 patent
`(Ex. 1001)
`
`’462 file history
`(Ex. 1002)
`
`’549 patent
`
`Banting
`
`Bell, Hamster Preproglucagon Contains the Sequence of
`Glucagon and Two Related Peptides, 302 NATURE 716
`(1983)
`
`Bell
`
`Highlights of Prescribing Information: Bydureon, Revised:
`01/2012
`
`Bydureon label
`
`Highlights of Prescribing Information: Byetta, Revised:
`10/2009
`
`Byetta label
`
`ClinicalTrials.gov Background, CLINICALTRIALS.GOV,
`https://clinicaltrials.gov/ct2/about-site/background
`(last
`visited Mar. 10, 2023)
`
`ClinicalTrials.gov
`Background
`
`Drab, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus: Current Status and Future Prospects, 30
`PHARMACOTHERAPY 609 (2010)
`
`Drab
`
`Drucker, Enhancing Incretin Action for the Treatment of
`Type 2 Diabetes, 26 DIABETES CARE 2929 (2003)
`
`Drucker 2003
`
`5
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 5
`
`

`

`Full Name of Cited Reference
`
`Drucker, The Incretin System: Glucagon-Like Peptide-1
`Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors in
`Type 2 Diabetes, 368 LANCET 1696 (2006)
`
`Abbreviation
`
`Drucker 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)
`
`Glaesner
`
`HARRISON’S PRINCIPLES OF INTERNAL MED., Chapter
`338(Fauci et al. eds. 17th ed. 2008)
`
`Harrison’s
`
`ClinicalTrials.gov,
`Award:
`https://ash.harvard.edu/news/clinicaltrials.gov (last visited
`Mar. 10, 2023)
`
`Harvard Award
`
`Holst, Truncated Glucagon-like Peptide I, an Insulin-
`Releasing Hormone from the Distal Gut, 211 (2) FEBS
`LETTERS 169 (1987)
`
`Holst 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)
`
`Holst 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)
`
`Jimenez-Solem
`
`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)
`
`Kim
`
`Kirillova,
`in
`Reporting
`and Outcome
`Results
`ClinicalTrials.gov, What Makes it Happen?, 7(6) PLoS ONE
`1 (2012)
`
`Kirillova
`
`6
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 6
`
`

`

`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)
`
`Abbreviation
`
`Knudsen 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 2004
`
`Knudsen, Liraglutide, a GLP-1 Analogue to Treat Diabetes
`in ANALOGUE-BASED DRUG DISCOVER II (Fischer &
`Ganellin eds. 2010)
`
`Knudsen 2010
`
`U.S. Patent No. 6,268,343
`
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus, 5 NATURE REV. ENDOCRINOLOGY 262 (2009)
`
`Knudsen patent
`
`Lovshin (Ex. 1012)
`
`Lund, Emerging GLP-1 Receptor Agonists, 16 EXPERT OP.
`ON EMERGING DRUGS 607 (2011)
`
`Lund
`
`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)
`
`Mojsov
`
`Monami, Effects of Glucagon-Like Peptide-1 Receptor
`Agonists on Body Weight: A Meta-Analysis, 2012
`EXPERIMENTAL DIABETES RSCH. 1 (2012)
`
`Monami
`
`NCT00167115, CLINICALTRIALS.GOV,
`https://www.clinicaltrials.gov/ct2/show/NCT00167115 (last
`visited Mar. 10, 2023)
`
`NCT115
`
`NCT01933490, CLINICALTRIALS.GOV,
`https://www.clinicaltrials.gov/ct2/show/NCT01933490 (last
`visited Mar. 10, 2023)
`
`NCT490
`
`Clinical Trial No. NCT00696657
`
`NCT657
`1013)
`
`(Ex.
`
`7
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 7
`
`

`

`Full Name of Cited Reference
`
`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)
`
`(Ex.
`
`Abbreviation
`
`NCT773
`1014)
`
`Nielsen
`
`Seino
`
`Tamimi, Drug Development: From Concept to Marketing!,
`113 NEPHRON CLINICAL PRAC. c125 (2009)
`
`Tamimi
`
`Tasneem, The Database
`for Aggregate Analysis of
`ClinicalTrials.gov (AACT) and Subsequent Regrouping by
`Clinical Specialty, 7(3) PLoS ONE 1(2012)
`
`Tasneem
`
`Victoza, PHYSICIANS’ DESK REFERENCE (65th ed. 2010)
`
`Victoza label
`
`Vilsbøll, Glucagon-Like Peptide-1 and Diabetes Treatment,
`21 INTERNATIONAL DIABETES MONITOR 1(2009).
`
`Vilsbøll
`
`International Patent Application Pub. No. WO 03/002136 WO136
`
`International Patent Application Pub. No. WO 2011/073328 WO328
`
`International Patent Application Pub. No. WO 2011/138421 WO421 (Ex. 1011)
`
`International Patent Application Publication No. WO
`91/11457
`
`WO457
`
`International Patent Application Pub. No. WO 2006/097537 WO537 (Ex. 1015)
`
`Zarin, The ClinicalTrials.gov Results Database—Update
`and Key Issues, 364 NEW ENGL. J. MED. 852 (2011)
`
`Zarin
`
`
`
`8
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 8
`
`

`

`1. My name is Melissa E. Weinberg, M.D. I have been retained by counsel
`
`for Petitioners Sun Pharmaceutical Industries Ltd. and Sun Pharmaceutical
`
`Industries Inc. (collectively “Sun”) 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 Sun 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, Sun will request that the United States Patent and Trademark Office
`
`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, John Bantle, MD submitted
`
`a declaration (Ex. 1003). I have reviewed Dr. Bantle’s declaration and agree with it.
`
`Therefore, I have adopted it and, accordingly, submit this expert declaration to
`
`address and support Sun’s IPR petition for the ’462 patent.
`
`I.
`
`QUALIFICATIONS AND BACKGROUND
`Education and Experience; Prior Testimony
`I am a board-certified endocrinologist at California Pacific Medical
`
`A.
`2.
`
`Center where I serve as Medical Director of Inpatient Diabetes. I have more than 15
`
`years of experience as an endocrinologist and have served as physician lead of Sutter
`
`Health’s Diabetes Clinical Improvement Community. I am also a Subject Matter
`
`Expert for diabetes and endocrinology for Sutter Health’s electronic medical record.
`
`9
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 9
`
`

`

`3.
`
`I earned a Bachelor of Arts degree in 1997 from Harvard College and a
`
`Doctor of Medicine degree in 2001 from Yale University. I completed an internship
`
`and my residency at Brigham & Women’s Hospital in 2002 and 2004, respectively.
`
`Thereafter, I was a fellow in endocrinology at the University of California, San
`
`Francisco through 2008.
`
`4.
`
`I have authored publications and made numerous presentations on the
`
`topic of diabetes at my institution, including education of other attending physicians,
`
`fellows, residents, and medical students. I have been involved in revising Sutter
`
`Health’s Type 2 Diabetes guidelines.
`
`5. My qualifications are further described on my curriculum vitae,
`
`attached as Exhibit 1092.
`
`B.
`10.
`
`Prior Testimony
`In the past four years, I have been a consulting expert in the following
`
`proceedings but offered no testimony in either:
`
`• Kalamas vs John Muir Health and Calvin Knight, Contra Costa Superior
`Court (2023); and
`• Radius Health, Inc. et al. vs Orbicular Pharmaceutical Technologies
`Private Limited, (D. Mass. 2023)
`Basis for Opinions and Materials Considered
`Exhibit A includes a list of the materials I considered, in addition to my
`
`C.
`1.
`
`experience, education, and training, to provide the opinions contained in this
`
`declaration.
`
`10
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 10
`
`

`

`Retention and Compensation
`D.
`11. Sun retained me as a technical expert to provide various opinions about
`
`the ’462 patent. I am being compensated at a rate of $600 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)
`
`b)
`
`c)
`
`d)
`
`e)
`
`Ground 1: WO421 anticipated claims 1-3 of the ’462
`patent;
`Ground 2: Lovshin anticipated claims 1-3 of the ’462
`patent;
`Ground 3: Claims 1–10 of the ’462 patent would have
`been obvious over WO421 in view of the ’424 publication;
`Ground 4: Claims 1–10 of the ’462 patent would have
`been obvious over WO537 in view of Lovshin; and
`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.
`
`11
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 11
`
`

`

`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 offered the opinion
`
`(Ex. 1007) that it would have been obvious to a POSA to formulate semaglutide into
`
`an isotonic 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
`
`12
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 12
`
`

`

`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.
`
`20.
`
`I have been informed that Sun 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.
`
`
`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.
`
`13
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 13
`
`

`

`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
`
`claimed invention and the prior art; (3) the level of ordinary skill in the art; and (4)
`
`secondary considerations of non-obviousness.
`
`24.
`
`I understand that when there is some recognized reason to solve a
`
`problem, and there are a finite number of identified, predictable and known
`
`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 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 field of endeavor at the
`
`time of invention or addressed by the patent can provide 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 obviousness.
`
`IV. PERSON OF ORDINARY SKILL IN THE ART
`25.
`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
`
`14
`
`SUN EXHIBIT 1091, IPR2024-00107, PAGE 14
`
`

`

`supplement my opinions on unpatentability if the Board adopts, or the parties agree
`
`to, a different definition of a skilled artisan.
`
`26. The subject matter of claims 1–10 of the ’462 patent falls within the
`
`medicinal chemical arts. A skilled artisan would have had (1) an M.D., a Pharm.D.,
`
`or a Ph.D. in pharmacy, chemical engineering, bioengineering, chemistry, or related
`
`discipline; (2) at least two years of experience in protein or peptide therapeutic
`
`development and/or manufacturing or diabetes treatments; and (3) experience with
`
`the development, design, manufacture, formulation, or administration of therapeutic
`
`agents, and the literature concerning protein or peptide formulation and design, or
`
`diabetes treatments.
`
`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
`
`experience in the area of 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, and the
`
`literature concerning protein or peptide formulation and design, or diabetes
`
`treatments.
`
`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
`
`the extent necessary, a skilled artisan may collaborate with one or more other skilled
`
`15
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`

`

`artisans for one or more aspects with which the other skilled artisan may have
`
`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
`
`higher degree of experience.
`
`29. As explained in this declaration and exemplified by the information
`
`provided in my CV (Ex. 1092), I met the qualifications of a skilled artisan for
`
`purposes of the claims of the ’462 patent.
`
`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.
`
`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
`
`patent for foreign reference EP12174535, listed under “Foreign Application Priority
`
`Data.” Therefore, I have been asked to assume that references pre-dating July 1,
`
`2012, are prior art. To the extent Patent Owner later asserts and/or proves that the
`
`claims are entitled to an earlier priority or invention date, I reserve the right to
`
`supplement this declaration.
`
`The ’462 patent’s claims
`A.
`32. The ’462 patent has one independent claim, which recites:
`
`16
`
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`
`

`

`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.
`
`33. Dependent claims 2–10 depend from claim 1, directly or indirectly, and
`
`are provided below.
`
`34. Dependent claim 2 recites:
`
`2.
`
`The method according to claim 1, wherein the
`
`semaglutide is administered by parenteral administration.
`
`35. Dependent claim 3 recites:
`
`3.
`
`The method according to claim 2, wherein the
`
`solution is administered by subcutaneous injection.
`
`36. Dependent claim 4 recites:
`
`4.
`
`The method according to claim 1, wherein the
`
`semaglutide is administered in the form of an isotonic
`
`aqueous solution comprising phosphate buffer at a pH in
`
`the range of 7.0-9.0.
`
`37. Dependent claim 5 recites:
`
`5.
`
`The method according to claim 4, wherein the
`
`solution further comprises propylene glycol and phenol.
`
`38. Dependent claim 6 recites:
`
`17
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`

`

`6.
`
`The method according to claim 4, wherein the pH is
`
`7.4.
`
`39. Dependent claim 7 recites:
`
`7.
`
`The method according to claim 6, wherein the
`
`solution further comprises propylene glycol and phenol.
`
`40. Dependent claim 8 recites:
`
`8.
`
`The method according to claim 4, wherein the
`
`phosphate buffer is a sodium dihydrogen phosphate
`
`buffer.
`
`41. Dependent claim 9 recites:
`
`9.
`
`The method according to claim 1, wherein the
`
`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
`
`propylene glycol and phenol.
`
`42. Dependent claim 10 recites:
`
`10. The method according to claim 9, wherein the pH is
`
`7.4.
`
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`

`

`The Prosecution History of the ’462 Patent
`B.
`43. When the application for the ’462 patent was filed on July 21, 2017,
`
`independent claim 1 recited:
`
`1.
`
`A method for
`
`b)
`
`c)
`
`reduction of HbA1c;
`treatment of type 2 diabetes, hyperglycemia, impaired
`glucose tolerance, or non-insulin dependent diabetes; or
`treatment of obesity, reducing body weight and/or food
`intake, or inducing satiety;
`wherein said method comprises administration of a GLP-
`
`d)
`
`1 agonist to a subject in need thereof, wherein said GLP-1
`
`agonist
`
`i)
`
`ii)
`
`has a half-life of at least 72 hours;
`
`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
`
`19
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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.
`
`
`the exhibit and not, for example, to the internal page numbering of a journal article,
`
`book chapter, or international patent application publication.
`
`20
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`

`

`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
`
`a)
`
`b)
`
`reduction of HbA1c;
`treatment of type 2 diabetes, hyperglycemia, impaired
`glucose tolerance, or non-insulin dependent diabetes; or
`treatment of obesity, reducing body weight and/or food
`intake, or inducing satiety;
`wherein said method comprises administration of a GLP-
`
`c)
`
`1 agonist to a subject in need thereof,
`
`wherein said GLP-1 agonist
`
`i)
`
`ii)
`
` has a half-life of at least 72 hours;
`
` 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 332 (January 23, 2019 listing of claims).
`
`47. Following this amendment, the applicants filed a terminal disclaimer
`
`over U.S. Patent No. 9,764,003, which the Examiner characterized as claiming “a
`
`method for reducing body weight, comprising administering semaglutide once
`
`21
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`
`

`

`weekly in an amount of at least 0.7 mg and up to 1.6 mg to a subject in need thereof,
`
`wherein said semaglutide is administered without another therapeutic agent.” See
`
`Ex. 1002 (File history) at 336 (February 28, 2019 Terminal disclaimer); id. at 317
`
`(July 23, 2018 Office Action describing U.S. Patent No. 9,764,003).
`
`48. The Examiner then withdrew the anticipation rejections and allowed
`
`the claims, stating:
`
`The ’657 clinical
`
`trial compared semaglutide and
`
`liraglutide in treatment of type 2 diabetic patients. The
`
`semaglutide or liraglutide was used as on add-on therapy
`
`to type 2 diabetic patients already taking metformin.
`
`Efficacy of treatment was further assessed by a reduction
`
`in HbA1c levels. Patients in the Arm Labels D and E of
`
`the clinical trial were administered 0.8 mg once weekly by
`
`subcutaneous injection. However, the reference does not
`
`teach or disclose a higher amount of 1 mg semaglutide.
`
`See Ex. 1002 (File history) at 344-44 (March 6, 2019 Notice of Allowability).
`
`49. The Examiner did not further consider the prior art or whether it would
`
`have anticipated or rendered obvious the amended claims. In particular, while the
`
`Examiner stated that NCT657 “does not teach or disclose” 1 mg semaglutide, the
`
`Examiner did not consider whether NCT657 rendered obvious that do