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`IPR2023-00724
`U.S. Patent 10,335,462
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`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 IPR2023-00724
`Patent 10,335,462
`______________________
`
`EXPERT DECLARATION OF PATRICK J. SINKO, PH.D.
`IN SUPPORT OF PATENT OWNER’S RESPONSE TO
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 10,335,462
`
`
`
`1
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`PROTECTIVE ORDER MATERIAL
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`Novo Nordisk Exhibit 2056
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
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`IPR2023-00724
`U.S. Patent 10,335,462
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`
`
`B.
`
`C.
`
`D.
`
`TABLE OF CONTENTS
`INTRODUCTION ........................................................................................ 1
`I.
`BACKGROUND AND QUALIFICATIONS ............................................. 2
`II.
`III. PRIORITY DATE AND ONE OF ORDINARY SKILL .......................... 6
`IV. MATERIALS RELIED UPON ................................................................... 9
`V.
`THE CHALLENGED CLAIMS AND OZEMPIC ................................... 9
`A.
`The Challenged Claims ........................................................................ 9
`B.
`Ozempic® (Semaglutide) ................................................................... 10
`C.
`Claim Construction ............................................................................ 12
`VI. OZEMPIC® PRACTICES CLAIMS 4-10 OF THE ’462 PATENT ..... 14
`A.
`Claim 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. ................................................................ 14
`Claim 2: The method according to claim 1, wherein the
`semaglutide is administered by parenteral administration. ................ 15
`Claim 3: The method according to claim 2, wherein the solution
`is administered by subcutaneous injection. ........................................ 16
`Claim 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. ...................................................................................................... 16
`Claim 5: The method according to claim 4, wherein the solution
`further comprises propylene glycol and phenol. ................................ 18
`Claim 6: The method according to claim 4, wherein the pH is 7.4.
` ............................................................................................................ 19
`Claim 7: The method according to claim 6, wherein the solution
`further comprises propylene glycol and phenol. ................................ 19
`Claim 8: The method according to claim 4, wherein the
`phosphate buffer is a sodium dihydrogen phosphate buffer. ............. 20
`Claim 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
`
`G.
`
`E.
`
`F.
`
`H.
`
`I.
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`i
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`IPR2023-00724
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`J.
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`wherein the solution further comprises propylene glycol and
`phenol. ................................................................................................ 21
`Claim 10: The method according to claim 9, wherein the pH is
`7.4. ...................................................................................................... 23
`VII. THE FORMULATION USED IN THE SUSTAIN 6 AND FLOW
`CLINICAL TRIALS PRACTICES CLAIMS 4-10 OF THE ’462
`PATENT ...................................................................................................... 23
`VIII. CONCLUSION ........................................................................................... 25
`
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`I, Patrick J. Sinko, hereby declare under penalty of perjury:
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`IPR2023-00724
`U.S. Patent 10,335,462
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`
`I.
`
`INTRODUCTION
`
`1.
`
`I have been retained by Groombridge, Wu, Baughman & Stone LLP,
`
`on behalf of Novo Nordisk A/S (“Novo Nordisk”) to provide assistance regarding
`
`U.S. Patent No. 10,335,462 (“the ’462 patent”). Specifically, I have been asked to
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`provide my opinions regarding the whether Ozempic® practices claims 1-10 of the
`
`’462 patent (the “Challenged Claims”) and whether the formulation used in the
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`SUSTAIN 6 and FLOW clinical trials practices claims 4-10. Except as otherwise
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`indicated, I have personal knowledge of the facts and opinions set forth in this
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`declaration. All statements herein made of my own knowledge are true and all
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`statements made on information and belief are believed to be true. If called upon to
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`do so, I would testify competently thereto.
`
`2.
`
`I am being compensated for my time at a rate of $950 per hour. I will
`
`be reimbursed for any expenses that I incur during the course of this work. My
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`compensation is not contingent upon the results of my study, the substance of my
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`opinions, or the outcome of any proceeding involving the Challenged Claims. I have
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`no financial interest in the outcome of this matter or in the pending litigations
`
`involving Novo Nordisk A/S and Novo Nordisk Inc.
`
`3.
`
`Except as otherwise indicated, I have personal knowledge of the facts
`
`set forth in this Declaration. All statements herein made of my own knowledge are
`
`1
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`true and all statements made on information and belief are believed to be true. If
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`called upon to do so, I would testify competently thereto.
`
`II. BACKGROUND AND QUALIFICATIONS
`
`4.
`
`I offer statements and opinions on behalf of Novo Nordisk, generally
`
`regarding Novo Nordisk’s commercial embodiment, Ozempic, formulations used in
`
`Novo Nordisk’s clinical trials, and the understanding of a person of ordinary skill in
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`the art as it relates to the Challenged Claims.
`
`5.
`
`I am a Distinguished Professor of Pharmaceutics in the Ernest Mario
`
`School of Pharmacy at Rutgers, The State University of New Jersey, where I was
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`Chair of the Department of Pharmaceutics from 1998 to 2008. I also served as the
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`Associate Vice President for Research at Rutgers from 2007 through 2019, where I
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`provided executive-level oversight of Comparative Medicine Resources, Research
`
`Core Facilities, In Vivo Research Services, Biomedical Advisory Committees, and
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`the Controlled Substances program for our three regional campuses. Since 2003, I
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`have held the Parke-Davis Endowed Chair in Pharmaceutics and Drug Delivery at
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`Rutgers.
`
`6.
`
`I am currently the immediate past President and member of the Board
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`of Directors of the American Association of Pharmaceutical Scientists (“AAPS”), a
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`professional, scientific organization with approximately 8,000 individual members
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`and over 12,000 actively participating stakeholders employed in academia, industry,
`
`2
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`government, and other pharmaceutical science related institutes worldwide. The
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`mission of the AAPS is to advance the capacity of pharmaceutical scientists to
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`develop products and therapies that improve global health.
`
`7.
`
`I received a BS in Pharmacy from Rutgers University in 1982 and
`
`completed my Ph.D. in Pharmaceutics at the University of Michigan in 1988. After
`
`completing my Ph.D., I continued as a Research Scientist at the University of
`
`Michigan until 1991.
`
`8.
`
`In 1991, I joined the faculty at Rutgers in the Department of
`
`Pharmaceutics as an Assistant Professor. I was promoted to the ranks of Associate
`
`Professor in 1997, Professor in 2000, and Distinguished Professor in 2007. As a
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`Professor at Rutgers, I have taught courses at both the graduate and undergraduate
`
`levels in several subjects, including Drug Delivery, General Toxicology,
`
`Pharmacology, and Pharmaceutics.
`
`9.
`
`At Rutgers, my research is generally directed to biopharmaceutics and
`
`pharmaceutical formulations. I have numerous active and completed projects
`
`sponsored by the National Institutes of Health (“NIH”) and the pharmaceutical
`
`industry relating to formulations and drug delivery systems. As such, I have
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`extensive experience in formulating and evaluating orally administered dosage
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`forms and their respective components and processes.
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`3
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`I have written and published extensively in the field of pharmaceutics,
`
`10.
`
`including authoring or co-authoring more than 185 peer-reviewed publications, 70
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`book chapters and monographs, and 283 abstracts. I have also given over 175
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`lectures at scientific meetings and conferences, universities, and companies. I have
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`been named as an inventor on 20 issued patents in the field of pharmaceutics.
`
`11.
`
`I am the Editor and Principal Author of the recent (5th through 7th) and
`
`current (8th, published in 2023) editions of Martin’s Physical Pharmacy and
`
`Pharmaceutical Sciences, which has been a well-recognized textbook in the
`
`Pharmaceutical Sciences since 1960, and is used extensively worldwide.
`
`12.
`
`I currently serve as Editor-in-Chief for the journal Pharmaceutics. I
`
`also serve or have served on the editorial advisory boards for Advanced Drug
`
`Delivery Reviews (2005-2010), Applied Nano, Molecular Pharmaceutics, Therapy
`
`(2004-2011), Biomedical Materials (2006-2010), Pharmaceutics, Recent Patents on
`
`Drug Delivery & Formulation, Current Drug Discovery Technologies, Journal of
`
`Drug Delivery Science and Technology, Journal of Drug Delivery, Drug Delivery
`
`and Translational Research, and Scientia Pharmaceutica.
`
`13. Throughout my academic career, I have received several awards,
`
`honors and recognitions. In 2003, I was elected a Fellow of the AAPS for being
`
`“internationally recognized as an expert in biopharmaceutics and drug delivery.” In
`
`2006, I was awarded MERIT status for my NIH research grant titled “Enhancing
`
`4
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`Brain & Intestinal Uptake of Anti-AIDS Drugs”. MERIT status is awarded to a
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`select number of NIH investigators (less than 5% of funded investigators) who have
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`demonstrated superior competence, outstanding productivity, and are leaders in their
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`fields with paradigm-shifting ideas. In 2011, I was elected Fellow of the American
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`Association for the Advancement of Science (“AAAS”) for distinguished
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`contributions to biopharmaceutics and innovative approaches for drug delivery and
`
`targeting, as well as academic leadership at Rutgers. In 2017, I was elected Fellow
`
`in the Controlled Release Society in recognition of “outstanding contributions to the
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`field of delivery science and technology.” In 2023, I was elected to the National
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`Academy of Inventors as a Fellow. In 2024, I was awarded the International Science
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`and Technology Cooperation Prize from the Fujian Provincial Government in China.
`
`14.
`
`I am extensively involved with the NIH as a grant reviewer, having
`
`served on over 70 review panels. I also served as a charter member of the
`
`Pharmacology Study Section, the Xenobiotic and Nutrient Disposition and Action
`
`Study Section, and the Developmental Therapeutics Study Section in the Center for
`
`Scientific Review. These study sections review research grant applications related
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`to drugs and drug delivery systems.
`
`15.
`
`In addition to my academic work, I have been a consultant to numerous
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`pharmaceutical and biotechnology companies including: Merck, Sharp and Dohme
`
`Corp., Alza Corporation, Wyeth Ayerst, Sandoz Pharmaceuticals Corp., Geneva,
`
`5
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`PROTECTIVE ORDER MATERIAL
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`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
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`Ribi ImmunoChem Research, Inc., Biogen Corporation, Novo Nordisk A/S
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`(Denmark), Uniroyal Chemical Company, Inc., Warner-Lambert Company, Glaxo-
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`Wellcome PLC, Teva Pharmaceuticals, USA, Trega Biosciences, Inc., Merck & Co.,
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`Eli Lilly & Co., Nobex Corp., Affymax, Spherics, Inc., Lion Bioscience, Inc., Abbott
`
`Laboratories, Syntonix, and Genteric. I have served on advisory panels for
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`Boehringer Ingelheim, Wyeth Ayerst, Lederle Laboratories, Novo Nordisk (US),
`
`and Abbott Laboratories. I served as a member of the Scientific Advisory Board for
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`Metacrine Sciences and as Chair of the Scientific Advisory Board for TheraPort
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`Biosciences.
`
`16. Attached hereto as Appendix A is a true and correct copy of my
`
`Curriculum Vitae describing my background and experience and includes a list of
`
`my publications, presentations, and expert testimony experience.
`
`III. PRIORITY DATE AND ONE OF ORDINARY SKILL
`
`17.
`
`I understand that a person of ordinary skill in the art (“POSITA”) is a
`
`hypothetical person who is presumed to have known the relevant art at the time of
`
`the invention. I understand that a POSITA is also a person of ordinary creativity,
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`who in many cases will be able to fit the teachings of multiple patents or printed
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`publications together. I further understand that the factors that may be considered
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`in determining the level of ordinary skill in a particular field of art include (1) the
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`level of education and experience of those working in the field, (2) the types of
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`problems encountered in the field, and (3) the sophistication of the technology at the
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`time of the invention, which I understand is March 17, 2010, or at least May 28,
`
`2010, as to claims 1-3 but in any event no later than July 1, 2012, for claims 1-3, and
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`no later than July 1, 2012, as to claims 4-10 (my opinions are the same under all of
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`these dates). I understand that not every factor may be present in every case. I
`
`understand that a POSITA is not a specific real person, but rather is a hypothetical
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`person having the qualities reflected by the above-discussed factors. I further
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`understand that a POSITA would have knowledge from the teachings of the prior
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`art, including the art cited herein.
`
`18.
`
`In my opinion, on or before July 1, 2012, a person of ordinary skill in
`
`the art to which the ’462 patent pertains would have an M.D. or, alternatively, a
`
`Ph.D. or equivalent degree in Pharmacology, Pharmaceutics, Biopharmaceutics, or
`
`a related field. The M.D. or Ph.D. would have 3-5 years of experience conducting
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`clinical research in the field of diabetes treatments, including in the design of dosing
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`regimens and dosage forms for type 2 diabetes treatments, or would have 3-5 years
`
`of research or
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`industry experience relating
`
`to developing pharmaceutical
`
`formulations and/or dosing regimens. Alternatively, the individual would be a
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`highly skilled scientist lacking a Ph.D. or M.D., but would have more than 5 years
`
`of experience conducting clinical research in the field of diabetes treatments. The
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`person of ordinary skill would consult, as appropriate with others having specific
`
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`expertise in pharmaceutical development, formulation, and manufacturing. Based
`
`on my education and experience, I meet this definition.
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`19.
`
`I understand that Mylan contends that a person having ordinary skill in
`
`the art to which the ’462 patent pertains would have (1) an M.D., Pharm.D., or Ph.D.
`
`in pharmacy, chemical engineering, bioengineering, chemistry, or related discipline;
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`(2) at least two years of experience in protein or peptide therapeutic development
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`and/or manufacturing or diabetes treatments; and (3) experience with the
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`development, design, manufacture, formulation, or administration of therapeutic
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`agents, and the literature concerning protein or peptide formulation and design, or
`
`diabetes treatments. Based on my education and experience, I meet this definition.
`
`20. My opinions would not change if Mylan’s definition of a POSITA,
`
`rather than my definition, was applied.
`
`21. Well before March 17, 2010, May 28, 2010, and July 1, 2012, my level
`
`of skill in the art was at least that of POSITA under either my definition or Mylan’s
`
`definition. I am qualified to provide opinions concerning what POSITA would have
`
`known and understood as of the priority date of the ’462 patent, and unless otherwise
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`stated, my analysis and conclusions herein are from the perspective of POSITA at
`
`least as of March 17, 2010. My opinions herein would be the same if the priority
`
`date were, instead, May 28, 2010, or July 1, 2012.
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`8
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`IV. MATERIALS RELIED UPON
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`IPR2023-00724
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`22.
`
`In reaching the conclusions described in this declaration, I have relied
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`on the documents and materials cited in this Declaration and those identified in
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`Appendix B. These materials are the patent, internal Novo Nordisk documents, and
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`printed publications. Each of these is a type of document that experts in my field
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`would reasonably rely upon when forming their opinions.
`
`23. My opinions are also based on my education, training, knowledge, and
`
`personal and professional experience.
`
`V. THE CHALLENGED CLAIMS AND OZEMPIC
`
`A. The Challenged Claims
`24. The Challenged Claims of the ’462 patent (claims 1-10) are listed
`
`below:
`
`[1] A method for treating type 2 diabetes, comprising administering semag-
`
`lutide once weekly in an amount of 1.0 mg to a subject in need thereof.
`
`[2] The method according to claim 1, wherein the semaglutide is adminis-
`
`tered by parenteral administration.
`
`[3] The method according to claim 2, wherein the solution is administered
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`by subcutaneous injection.
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`[4] The method according to claim 1, wherein the semaglutide is adminis-
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`tered in the form of an isotonic aqueous solution comprising phosphate
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`buffer at a pH in the range of 7.0-9.0.
`
`[5] The method according to claim 4, wherein the solution further comprises
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`propylene glycol and phenol.
`
`[6] The method according to claim 4, wherein the pH is 7.4.
`
`[7] The method according to claim 6, wherein the solution further comprises
`
`propylene glycol and phenol.
`
`[8] The method according to claim 4, wherein the phosphate buffer is a so-
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`dium dihydrogen phosphate buffer.
`
`[9] The method according to claim 1, wherein the semaglutide is adminis-
`
`tered 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
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`phenol.
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`[10] The method according to claim 9, wherein the pH is 7.4.
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`B. Ozempic® (Semaglutide)
`25. Ozempic® is Novo Nordisk’s once-weekly type 2 diabetes treatment.
`
`EX2069, 1 (Ozempic® current label). Ozempic® was approved for sale in the
`
`United States in 2017. EX2069, 1 (Ozempic® current label). At approval, there
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`were three subcutaneous doses available, each administered once weekly: a 0.25 mg
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`treatment initiation dose (used to titrate patients up to a once-weekly maintenance
`
`dose) and 0.5 mg and 1.0 mg maintenance doses. EX2072, 1 (Ozempic® 2017
`
`label).
`
`26. As explained below, it is my opinion that Ozempic® practices at least
`
`claims 1-10 of the ’462 patent. EX 2018, 129:8-131:14 (confirming Ozempic®
`
`practices claims 1-3).
`
`27. The Ozempic® label instructs prescribers to “[s]tart at 0.25 mg once
`
`weekly. After 4 weeks, increase the dose to 0.5 mg once weekly” and “[i]f additional
`
`glycemic control is needed, increase the dose to 1 mg once weekly after at least 4
`
`weeks on the 0.5 mg dose.” EX2069, 1 (Ozempic® current label); EX2072, 1
`
`(Ozempic® 2017 label). The Ozempic® label states that Ozempic® is a “clear,
`
`colorless solution” that is “injected subcutaneously,” which is a form of parenteral
`
`administration. EX2069, §2.2 (Recommended Dosage), §3 (Dosage Forms and
`
`Strengths) (Ozempic® current label); EX2072, 11 (Ozempic® 2017 label).
`
`28. The label further states: “OZEMPIC is a sterile, aqueous, clear,
`
`colorless solution. Each pre-filled pen contains a 1.5 mL or a 3mL solution of
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`OZEMPIC equivalent to 2mg semaglutide, a 3mL solution of OZEMPIC equivalent
`
`to 4 mg of semaglutide, or a 3 mL solution of OZEMPIC equivalent to 8 mg of
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`semaglutide. Each 1 mL of OZEMPIC solution contains 0.68 mg, 1.34 mg or 2.68
`
`11
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`mg of semaglutide and the following inactive ingredients: disodium phosphate
`
`dihydrate, 1.42 mg; propylene glycol, 14.0 mg; phenol, 5.50 mg; and water for
`
`injections. OZEMPIC has a pH of approximately 7.4. Hydrochloric acid or sodium
`
`hydroxide may be added to adjust pH.” EX2072, 11 (Ozempic® 2017 label);
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`EX2069, 4 (§11).1
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`C. Claim Construction
`29.
`I understand that, for purposes of inter partes review, claim terms are
`
`construed in accordance with their ordinary and customary meaning. I understand
`
`claim construction begins with the claim language itself. Claim terms are presumed
`
`to have their ordinary and customary meaning in light of the patent’s specification
`
`as understood by persons of skill at the time of invention, unless (1) the patentee sets
`
`out a definition and acts as his own lexicographer, or (2) the patentee disavows the
`
`full scope of a claim term either in the specification or during prosecution. I
`
`understand that the “ordinary and customary” meaning of a claim term is the
`
`meaning that the term would have to persons of skill at the time of the invention,
`
`and that in addition to the claim language, the terms are also understood in the
`
`context of the patent’s specification and file history.
`
`
`
` For convenience, I cite to EX2072 for my analysis below, but it is equally sup-
`
` 1
`
`ported by EX2069, the current label.
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`I have been instructed to assume that “a method for treating type 2
`
`30.
`
`diabetes” means “the claimed administration is for the purpose of care and
`
`management of a patient with Type 2 diabetes” or “the claimed administration is
`
`intended to care for and manage a patient with Type 2 diabetes.” I understand
`
`that the ’462 patent states that “[i]n one embodiment the term ‘treatment’ or
`
`‘treating’ as used herein means the management and care of a patient for the purpose
`
`of combating a condition, such as a disease or a disorder. In one embodiment the
`
`term ‘treatment’ or ‘treating’ is intended to include the full spectrum of treatments
`
`for a given condition from which the patient is suffering, such as administration of
`
`the active compound to alleviate the symptoms or complications; to delay the
`
`progression of the disease, disorder or condition; to alleviate or relieve the symptoms
`
`and complications; and/or, to cure or eliminate the disease, disorder, or condition as
`
`well as to prevent the condition.” EX1001 (’462), 5:16-27. I have applied this
`
`meaning in my analysis of the claims.
`
`31. My opinions herein do not depend on “a method for treating type 2
`
`diabetes” requiring any particular degree of efficacy. I reserve the right to
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`supplement my analysis should Mylan argue or the Board adopt a different
`
`construction for this term.
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`13
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`IPR2023-00724
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`32. For all other terms, I have been asked to assume that they have their
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`plain and ordinary meaning as they would have been understood by persons of skill
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`in light of the specification.
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`VI.
`
` OZEMPIC® PRACTICES CLAIMS 4-10 OF THE ’462 PATENT
`
`A. Claim 1: A method for treating type 2 diabetes, comprising admin-
`istering semaglutide once weekly in an amount of 1.0 mg to a subject in
`need thereof.
`33. Claim 1 requires that the method be used for “treating type 2 diabetes.”
`
`The Ozempic® label states that “OZEMPIC is a glucagon-like peptide 1 (GLP-1)
`
`receptor agonist indicated as an adjunct to diet and exercise to improve glycemic
`
`control in adults with type 2 diabetes mellitus.” EX2072, 1 (Ozempic® 2017 label).
`
`The Ozempic® label further discloses that “Semaglutide reduces fasting and
`
`postprandial glucose concentrations. In patients with type 2 diabetes, treatment with
`
`semaglutide 1 mg resulted in reductions in glucose in terms of absolute change from
`
`baseline and relative reduction compared to placebo of 29 mg/dl (22%) for fasting
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`glucose, 74 mg/dL (36%) for 2 hour postprandial glucose, and 30 mg/dL (22%) for
`
`mean 24 hour glucose concentration.” EX2072, 12 (Ozempic® 2017 label).
`
`POSITA would have understood this to disclose “treating type 2 diabetes” under
`
`either party’s construction, as the label discloses administering Ozempic® for the
`
`intent or purpose of treating diabetes, including by, e.g., improving glycemic control
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`and reducing glucose.
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`14
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`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
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`34. Claim 1 further requires “administering semaglutide once weekly in an
`
`amount of 1.0 mg to a subject in need thereof.” The Ozempic® label states that “[if]
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`after at least 4 weeks additional glycemic control is needed, increase to 1 mg once
`
`weekly” and “[a]dminister once weekly.” EX2072, 1 (Ozempic® 2017 label). And
`
`“OZEMPIC” is defined as a “(semaglutide) injection.” EX2072, 1 (Ozempic® 2017
`
`label); see also 16-22 (discussing clinical trial results). POSITA would also have
`
`understood this administration would be administered to a patient in need, which, as
`
`described by the label, is an “adult[] with type 2 diabetes mellitus.” EX2072, 1
`
`(Ozempic® 2017 label).
`
`35. Thus, it is my opinion that Ozempic® practices claim 1. EX 2018,
`
`129:8-131:14 (confirming Ozempic® practices claims 1-3).
`
`B. Claim 2: The method according to claim 1, wherein the semaglutide
`is administered by parenteral administration.
`36. As stated above, it is my opinion that administration Ozempic®
`
`practices the limitations of claim 1.
`
`37. Claim 2 further requires that the “semaglutide is administered by
`
`parenteral administration.” The Ozempic® label states that Ozempic® is a “sterile,
`
`aqueous, clear, colorless solution” that is “inject[ed] subcutaneously.” EX2072, 1
`
`(Dosage and Administration), 11 (Description) (Ozempic® 2017 label). POSITA
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`15
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`IPR2023-00724
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`would have understood that subcutaneous injection is a form of parenteral
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`administration.
`
`38. Thus, it is my opinion that Ozempic® practices claim 2. EX 2018,
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`129:8-131:14 (confirming Ozempic® practices claims 1-3).
`
`C. Claim 3: The method according to claim 2, wherein the solution is
`administered by subcutaneous injection.
`39. As stated above, it is my opinion that administration Ozempic®
`
`practices the limitations of claim 2.
`
`40. Claim 3 further requires that the “solution is administered by
`
`subcutaneous injection.” The Ozempic® label states that Ozempic® is a “sterile,
`
`aqueous, clear, colorless solution” that is “inject[ed] subcutaneously.” EX2072, 1
`
`(Dosage and Administration), 11 (Description) (Ozempic® 2017 label).
`
`41. Thus, it is my opinion that Ozempic® practices claim 3. EX 2018,
`
`129:8-131:14 (confirming Ozempic® practices claims 1-3).
`
`D. Claim 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.
`42. As stated above, it is my opinion that administration of Ozempic®
`
`practices the limitations of claim 1.
`
`43. Claim 4 further requires that “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.” The Ozempic® label states that Ozempic® is a “sterile, aqueous,
`16
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`IPR2023-00724
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`clear, colorless solution” that is “inject[ed] subcutaneously.” EX2072, 1 (Dosage
`
`and Administration), 11 (Description) (Ozempic® 2017 label).
`
`44. Ozempic® is also isotonic. Isotonic means that the formulation has the
`
`same osmotic pressure, osmolarity, and osmolality as compared to that of the
`
`physiological fluid it is being compared to. EX1007, ¶70.
`
`
`
` Ozempic®, as described on the label, is an
`
`isotonic solution. EX2021, 4 (
`
`
`
`); EX2073, 1 (pharmaceutical form)
`
`(“electronic medicines compendium” entry for Ozempic®, identifying it as
`
`“isotonic”); EX2074, 1 (Ozempic® label in Australia, identifying it as “isotonic”).
`
`POSITA would have understood this to mean that
`
` the Ozempic® formulation, were isotonic,
`
`. EX2021, 4.
`
`
`
`
`
`
`
`.”
`
`45. The Ozempic® label further states that: “Each 1 mL of OZEMPIC
`
`solution contains 0.68 mg, 1.34 mg or 2.68 mg of semaglutide and the following
`
`inactive ingredients: disodium phosphate dihydrate, 1.42 mg… Hydrochloric acid or
`
`sodium hydroxide may be added to adjust pH.” EX2072, 4 (§11) (Ozempic® 2017
`
`label). Thus, when hydrochloric acid is added to the disodium phosphate dihydrate,
`
`a sodium dihydrogen phosphate buffer is formed.
`
`
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`17
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` Ozempic®, as described on the label, has a sodium
`
`dihydrogen phosphate buffer. EX2021, 4. “Disodium phosphate, dihydrate”
`
`“Hydrochloric acid”
`
`and
`
`
`
`
`
`
`
`pH to 7.4. EX2021, 4. POSITA would have understood this to mean that the sodium
`
`dihydrogen phosphate weak acid buffer pair would be formed to complete the
`
`sodium dihydrogen phosphate buffer. Thus, Ozempic® has a phosphate buffer.
`
`46. The Ozempic® label also states that: “OZEMPIC has a pH of
`
`approximately 7.4.” EX2072, 11 (Ozempic® 2017 label). A pH of approximately
`
`7.4 is between 7.0-9.0.
`
`47. Thus, it is my opinion that Ozempic® practices claim 4.
`
`E. Claim 5: The method according to claim 4, wherein the solution
`further comprises propylene glycol and phenol.
`48. As discussed above, it is my opinion that Ozempic® practices the
`
`limitations of claim 4.
`
`49. Claim 5 further requires that “the solution further comprises propylene
`
`glycol and phenol.” The Ozempic® label states “Each 1 mL of OZEMPIC solution
`
`contains 0.68 mg, 1.34 mg or 2.68 mg of semaglutide and the following inactive
`
`ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14.0 mg;
`
`phenol, 5.50 mg; and water for injections.” EX2072, 11 (Ozempic® 2017 label).
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`18
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`IPR2023-00724
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`50. Thus, it is my opin