UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________
`
`APOTEX INC.,
`Petitioner
`
`v.
`
`NOVO NORDISK A/S,
`PATENT OWNER
`_____________________
`
`CASE IPR2024-00631
`U.S. PATENT NO. 10,335,462
`ISSUED: JULY 2, 2019
`
`TITLE:
`USE OF LONG-ACTING GLP-1 PEPTIDES
`
`DECLARATION OF JUDITH KORNER, M.D., Ph.D.
`
`March 1, 2024
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0001
`
`

`

`TABLE OF CONTENTS
`
`Page
`TABLE OF CONTENTS ........................................................................................ i 
`TABLE OF ABBREVIATIONS ............................................................................. v 
`I. 
`QUALIFICATIONS AND BACKGROUND .............................................. 1 
`A. 
`Education and Experience ..................................................................... 1 
`B. 
`Basis for Opinions and Materials Considered ....................................... 4 
`C. 
`Retention and Compensation ................................................................ 4 
`SUMMARY OF OPINIONS ......................................................................... 5 
`II. 
`III.  LEGAL STANDARDS .................................................................................. 7 
`IV.  PERSON OF ORDINARY SKILL IN THE ART ...................................... 8 
`V. 
`THE ’462 PATENT (Ex.1001) AND ITS CLAIMS .................................. 10 
`VI.  CLAIM CONSTRUCTION ........................................................................ 16 
`VII.  BACKGROUND ON DIABETES AND THE USE OF GLP-1
`DERIVATIVES FOR THE TREATMENT OF DIABETES .................. 18 
`A.  Diabetes Generally .............................................................................. 18 
`B. 
`Diabetes Treatment .............................................................................. 20 
`C. 
`The Use of GLP-1 Derivatives to Treat Diabetes ............................... 22 
`D.  Use of Liraglutide to Treat Diabetes ................................................... 24 
`E. 
`Extended-Use GLP-1 Receptor Agonists ............................................ 27 
`VIII.  SCOPE AND CONTENT OF THE PRIOR ART .................................... 36 
`A. 
`Lovshin (Ex.1012) ............................................................................... 37 
`B. 
`U.S. Patent Application Pub. No. US2007/0010424 (Ex.1016) ......... 39 
`C.  WO 2006/097537 (Ex.1015) ............................................................... 43 
`D.  WO 2011/138421 (Ex.1011) ............................................................... 48 
`E. 
`Semaglutide Clinical Trial Records .................................................... 51 
`1. 
`Clinical Trial No. NCT00696657 (Ex.1013) ............................ 51 
`2. 
`Clinical Trial No. NCT00851773 (Ex.1014) ............................ 53 
`3. 
`ClinicalTrials.gov is a Part of the POSA’s Knowledge ............ 55 
`
`-i-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0002
`
`

`

`F. 
`
`B. 
`
`Other Art that Informs the POSA’s Knowledge ................................. 62 
`1. 
`Drucker 2003 (Ex.1023) ........................................................... 62 
`2. 
`Holst 2004 (Ex.1028) ................................................................ 63 
`3. 
`Knudsen 2001 (Ex.1031) .......................................................... 66 
`4. 
`Knudsen 2004 (Ex.1032) .......................................................... 70 
`5. 
`Knudsen patent (U.S. Patent No. 6,268,343) (Ex.1034) ........... 74 
`6. 
`Lund (Ex.1035) ......................................................................... 79 
`7. 
`Victoza label (Ex.1039) ............................................................ 79 
`8.  WO 03/002136 (Ex.1041) ......................................................... 82 
`9. 
`Additional prior art and references ........................................... 86 
`IX.  UNPATENTABILITY OF THE CLAIMS OF THE ’462
`PATENT ....................................................................................................... 87 
`A.  Ground 1: WO421 Anticipated Claims 1-3 ........................................ 87 
`1.  WO421 anticipated independent claim 1 .................................. 87 
`2.  WO421 anticipated claim 2 ...................................................... 99 
`3.  WO421 anticipated claim 3 ....................................................101 
`Ground 2: Lovshin Anticipated Claims 1-3 ......................................103 
`1. 
`Lovshin anticipated independent claim 1 ...............................103 
`a. 
`Lovshin disclosed the preamble of claim 1 ..................103 
`b. 
`Lovshin disclosed the element “comprising
`administering semaglutide” ..........................................104 
`Lovshin disclosed the element “once weekly in an
`amount of 1.0 mg” ........................................................105 
`Lovshin disclosed the element “to a subject in need
`thereof” .........................................................................108 
`Lovshin anticipated claim 2 ....................................................109 
`Lovshin anticipated claim 3 ....................................................110 
`Claim 1 of the ’462 patent would have been obvious over
`WO421 alone ..........................................................................110 
`
`-ii-
`
`2. 
`3. 
`4. 
`
`c. 
`
`d. 
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0003
`
`

`

`a. 
`
`b. 
`
`b. 
`
`5. 
`
`6. 
`
`2. 
`
`3. 
`
`C. 
`
`A skilled artisan would have been motivated to
`pursue the method recited in claim 1 ............................111 
`A skilled artisan would have had a reasonable
`expectation of success treating type 2 diabetes with
`a once weekly, 1.0 mg dose of semaglutide .................115 
`Claims 2 and 3 of the ’462 patent would have been
`obvious over WO421 alone ....................................................118 
`Claims 4-10 of the ’462 patent would have been obvious
`over WO421 in view of the ’424 publication .........................121 
`Ground 4: Claims 1-10 of the ’462 patent would have been
`obvious over WO537 in view of Lovshin .........................................122 
`1. 
`Claim 1 of the ’462 patent would have been obvious over
`WO537 in view of Lovshin .....................................................122 
`a. 
`A skilled artisan would have been motivated to
`pursue the method recited in claim 1 ............................122 
`A skilled artisan would have had a reasonable
`expectation of success treating type 2 diabetes with
`a once weekly, 1.0 mg dose of semaglutide .................127 
`Claims 2 and 3 of the ’462 patent would have been
`obvious over WO537 in view of Lovshin ...............................130 
`Claims 4-10 of the ’462 patent would have been obvious
`over WO537 in view of Lovshin ............................................132 
`D.  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 ......................................................................133 
`1. 
`Claim 1 of the ’462 patent would have been obvious over
`NCT657 in view of NCT773 ..................................................133 
`a. 
`A skilled artisan would have been motivated to
`pursue the method recited in claim 1 ............................137 
`A skilled artisan would have had a reasonable
`expectation of success treating type 2 diabetes with
`a once weekly, 1.0 mg dose of semaglutide .................143 
`
`b. 
`
`
`-iii-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0004
`
`

`

`2. 
`
`3. 
`
`E. 
`
`Claims 2 and 3 of the ’462 patent would have been
`obvious over NCT657 in view of NCT773 ............................149 
`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 ................................................................151 
`No Secondary Considerations Overcome Prima Facie
`Obviousness .......................................................................................152 
`1. 
`No unexpected results .............................................................152 
`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 ..........153 
`X.  RESERVATION OF RIGHTS .................................................................153 
`
`
`
`
`
`
`-iv-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0005
`
`

`

`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)
`
`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
`
`
`-v-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0006
`
`

`

`Full Name of Cited Reference
`Glaesner, Engineering and Characterization of the Long-
`Acting Glucagon-Like Peptide-1 Analogue LY2189265, an
`Fc Fusion Protein, 26 DIABETES/
`METABOLISM RSCH. & REV. 287 (2010)
`HARRISON’S PRINCIPLES OF INTERNAL MED.,
`Chapter 338
`(Fauci et al. eds. 17th ed. 2008)
`Award: ClinicalTrials.gov,
`https://ash.harvard.edu/news/clinicaltrialsgov (last visited
`Mar. 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)
`
`Abbreviation
`Glaesner
`
`Harrison’s
`
`Harvard Award
`
`Holst 1987
`
`Holst 2004
`
`Jimenez-Solem
`
`Kim
`
`Kirillova
`
`Knudsen 2001
`
`
`-vi-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0007
`
`

`

`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, a GLP-1 Analogue to Treat
`Diabetes in ANALOGUE-BASED DRUG
`DISCOVERY II
`(Fischer & Ganellin eds. 2010)
`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/NCT0016711
`5 (last visited Mar. 10, 2023)
`NCT01933490, CLINICALTRIALS.GOV,
`https://www.clinicaltrials.gov/ct2/show/NCT0193349
`0 (last visited Mar. 10, 2023)
`Clinical Trial No. NCT00696657
`
`Clinical Trial No. NCT00851773
`
`Abbreviation
`Knudsen 2004
`
`Knudsen 2010
`
`Knudsen patent
`Lovshin
`(Ex.1012)
`
`Lund
`
`Mojsov
`
`Monami
`
`NCT115
`
`NCT490
`
`NCT657
`(Ex.1013)
`NCT773
`(Ex.1014)
`
`
`-vii-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0008
`
`

`

`Abbreviation
`Nielsen
`
`Seino
`
`Tasneem
`
`Victoza label
`
`Vilsbøll
`
`Tamimi
`
`Full Name of Cited Reference
`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)
`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)
`
`WO421
`(Ex.1011)
`WO457
`
`WO537
`(Ex.1015)
`Zarin
`
`
`-viii-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0009
`
`

`

`I, Judith Korner, M.D., Ph.D. of New York, NY, declare as follows:
`
`
`1.
`
`I have been retained by counsel for Petitioner Apotex Inc. (“Apotex”).
`
`I understand that Apotex 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 Apotex is requesting that the
`
`United States Patent and Trademark Office (“USPTO”) cancel all claims of the
`
`’462 patent as unpatentable. I submit this expert declaration in support of
`
`Apotex’s IPR petition for the ’462 patent. I also understand that Mylan
`
`Pharmaceuticals Inc. has filed an IPR with respect to the ’462 patent in IPR2023-
`
`00724 (the “Mylan IPR”), which the Board has instituted. In support of the Mylan
`
`IPR, John Bantle, M.D., submitted a declaration (Ex.1003). I have reviewed and
`
`considered Dr. Bantle’s declaration. I agree with Dr. Bantle’s opinions set forth in
`
`his declaration, so I have adopted them. Accordingly, I submit this expert
`
`declaration in support of Apotex’s IPR petition for the ’462 patent.
`
`I.
`
`QUALIFICATIONS AND BACKGROUND
`A. Education and Experience
`2.
`I received my B.A. from Barnard College, Columbia University, in
`
`1979. Thereafter, I obtained a Ph.D. in Biochemistry and Molecular Biophysics
`
`from Columbia University in 1992. I then earned my M.D. from the College of
`
`Physicians & Surgeons at Columbia University in 1993. Following my education,
`
`-1-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0010
`
`

`

`I pursued postdoctoral training at Columbia Presbyterian Medical Center. I first
`
`served as a Resident in Internal Medicine from July 1993 to June 1996 and then
`
`served as Chief Resident and Clinical Assistant Physician in Internal Medicine
`
`from July 1996 to June 1997. I then became a Post-Doctoral Clinical Fellow in
`
`Endocrinology from July 1997 to November 1999.
`
`3.
`
`At Columbia University, I started as an Instructor (Chief Resident) in
`
`Clinical Medicine in July 1996 and later progressed to become an Assistant
`
`Professor of Clinical Medicine in December 1999. I held positions such as
`
`Associate Professor of Medicine (11/2010 - 03/2015) and currently serve as a
`
`Professor of Medicine at Columbia University Medical Center since March 2015.
`
`My hospital affiliations include being an Attending Physician at Columbia
`
`Presbyterian Medical Center (07/1996 - 06/1997) and New York
`
`Presbyterian/Columbia University Medical Center (12/1999 - present). Since July
`
`2006, I have directed the Metabolic and Weight Control Center at Columbia
`
`University Medical Center, recognized among the top 15 Medical Weight Loss
`
`Centers in the United States by Health Magazine in 2014.
`
`4.
`
`I am a licensed physician in the state of New York (License
`
`204016-1) since November 30, 2023. I am board-certified, holding Diplomate
`
`status with the American Board of Internal Medicine (1996), American Board of
`
`Endocrinology (1999, 2011), and American Board of Obesity Medicine (2014). In
`
`-2-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0011
`
`

`

`2010-2011, I received the Diabetes and Endocrinology Research Center (DERC)
`
`Pilot and Feasibility Award.
`
`5.
`
`Among various committee memberships, I have been an active
`
`committee member for the Certification of Obesity Medicine examination (2009-
`
`2010) and am currently a member of the Endocrine Society, American Diabetes
`
`Association, and a Fellow of The Obesity Society. I serve as an ad hoc reviewer
`
`for numerous journals, including Diabetes and Diabetes, Obesity, and Metabolism.
`
`I have also contributed to NIH Study Sections. I am chair of the American Board
`
`of Obesity Medicine Board of Directors.
`
`6.
`
`I have been actively involved in various committees at Columbia,
`
`including the Clinical Trials Advisory Committee (since 2008),
`
`Clinical/Epidemiological Research Committee (since 2012), and as the Director of
`
`the Pilot & Feasibility Award Program at the NY Nutrition Obesity Research
`
`Center (since 2015). I also serve on DSMB (Data and Safety Monitoring Board)
`
`for specific research projects.
`
`7.
`
`I have contributed to clinical research. Among other contributions, I
`
`served as the Principal Investigator for the analysis of peptides and metabolites
`
`after weight loss in humans with and without Type 2 Diabetes (12/2009 - 12/2011),
`
`sponsored by NGM Biopharmaceuticals. Additionally, I was the Co-Principal
`
`Investigator for a project on the prevention and treatment of obesity and diabetes
`
`-3-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0012
`
`

`

`using injectable brown adipose microtissues (02/2014 - 01/2015), sponsored by
`
`Coulter-Columbia Translational Research Partnership. And I have served as an
`
`investigator of several studies sponsored by the National Institutes of Health,
`
`including a study of the effects of leptin on body weight and neuroendocrine axes
`
`after gastric bypass (04/2008 - 03/2011), in which I was Principal Investigator, and
`
`a study of the feasibility of a weight loss intervention among female cancer
`
`survivors in SWOG (07/2011 - 06/2013).
`
`8.
`
`I am well familiar with GLP-1 and co-authored a publication titled
`
`“Postprandial hyperinsulinemia, exaggerated GLP-1 and blunted GIP secretion are
`
`associated with gastric bypass but not gastric banding” in the journal “Surg. Obes.
`
`Relat. Dis.” in 2007.
`
`9.
`
`A summary of my education, experience, publications, awards and
`
`honors, patents, publications, and presentations is provided in my CV, a copy of
`
`which is provided as Ex.1502.
`
`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. Apotex retained me as a technical expert to provide various opinions
`
`-4-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0013
`
`

`

`about the ’462 patent. I am being compensated at a rate of $750 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)
`
`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
`c)
`obvious over WO421 in view of the ’424 publication;
`
`Ground 4: Claims 1-10 of the ’462 patent would have been
`d)
`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,
`
`-5-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0014
`
`

`

`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 Apotex’s formulation expert Dr. Hugh Smyth is
`
`offering the opinion 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
`
`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.
`
`-6-
`
`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0015
`
`

`

`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 Apotex bears the burden of proving
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`unpatentability by a preponderance of the evidence. I have been told that this
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`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
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`technology of the patent as of the patent’s priority date.
`
`22.
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`I am told that for a patent to be anticipated, a prior art reference must
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`disclose all elements of that claim expressly and/or inherently as arranged in the
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`claim.
`
`23.
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`I am told that the concept of patent obviousness involves four factual
`
`
`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.
`
`-7-
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`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0016
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`

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`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)
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`secondary considerations of non-obviousness.
`
`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
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`sense. I understand that any need or problem known in the field of endeavor at the
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`time of invention or addressed by the patent can provide a reason for combining
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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.
`
`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
`
`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
`
`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,
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`-8-
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`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0017
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`

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`chemistry, or related discipline; (2) at least two years of experience in protein or
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`peptide therapeutic development and/or manufacturing or diabetes treatments; and
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`(3) experience with the development, design, manufacture, formulation, or
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`administration of therapeutic agents, and the literature concerning protein or
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`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
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`or more other skilled 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
`
`-9-
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`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0018
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`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.
`
`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
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`’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
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`the patent for foreign reference EP12174535, listed under “Foreign Application
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`Priority Data.” Therefore, I have been asked to assume that references pre-dating
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`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.
`
`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 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:
`
`-10-
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`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0019
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`

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`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:
`
`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:
`
`-11-
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`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0020
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`

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`10. The method according to claim 9, wherein the pH is 7.4.
`B.
`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:
`
`c)
`
`1. A method for
`a)
`reduction of HbA1c;
`b)
`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-1 agonist to a
`subject in need thereof, wherein said GLP-1 agonist
`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
`is administered once weekly or less often.
`Ex.1002 (File history) at 8.2
`
`i)
`ii)
`
`44. The Examiner rejected the filed claims on July 23, 2018, for
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`indefiniteness of claim language, anticipation in view of the prior art, and double
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`patenting over U.S. Patent No. 9,764,003. Id. at 307-18. On the merits of the
`
`
`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.
`
`-12-
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`Apotex v. Novo - IPR2024-00631
`Petitioner Apotex Exhibit 1501-0021
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`

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`anticipation rejections, the Examiner asserted that NCT00696657, which disclosed
`
`the use of semaglutide and liragluti