`
`IN THE UNITED STATES DISTRICT COURT
`
`FOR THE DISTRICT OF DELAWARE
`
`IN RE OZEMPIC (SEMAGLUTIDE) PATENT
`LITIGATION
`
`C.A. No. 22-md-3038-CFC
`
`CONFIDENTIAL
`
`NOVO NORDISK INC. AND NOVO
`NORDISK A/S,
`
`
`
`
`
`
`Plaintiffs/Counterclaim Defendants,
`
`v.
`
`
`RIO BIOPHARMACEUTICALS INC., et al.,
`
`
`
`Defendants/Counterclaim Plaintiffs.
`
`
`
`
`
`NOVO NORDISK INC. AND NOVO
`NORDISK A/S,
`
`Plaintiffs/Counterclaim Defendants,
`v.
`
`
`MYLAN PHARMACEUTICALS INC.,
`
`Defendants/Counterclaim Plaintiffs.
`
`C.A. No. 22-294-CFC
`
`C.A. No. 22-cv-1040-CFC
`
`
`
`Opening Expert Report of Dr. Paul Dalby
`Regarding Invalidity of U.S. Patent No. 10,335,462
`
`
`
`Novo Nordisk Exhibit 2026
`Dr. Reddy's Lab'ys, Inc. v. Novo Nordisk A/S
`IPR2024-00009
`Page 00001
`
`

`

`TABLE OF CONTENTS
`
`
`Page
`
`
`I.
`
`Qualifications and Background ...................................................................... 1
`A.
`Education and Experience; Prior Testimony........................................ 1
`B.
`Basis for Opinions and Materials Considered ...................................... 5
`C.
`Retention and Compensation ............................................................... 6
`Summary of Opinions ..................................................................................... 6
`II.
`III. Legal Standards .............................................................................................. 8
`IV. Person of Ordinary Skill in the Art ............................................................... 10
`V.
`The ’462 Patent And Asserted Claims 4, 5, 7 .............................................. 13
`A.
`The Formulation Claims of the ’462 Patent ....................................... 13
`B.
`The Prosecution History of the ’462 Patent ....................................... 14
`VI. Claim Construction ....................................................................................... 17
`VII. Background on GLP-1 Compound Formulations Used to Treat
`Diabetes ........................................................................................................ 19
`A.
`Parenteral formulations and components thereof were well-
`known ................................................................................................. 19
`GLP-1 compounds were well-known ................................................. 20
`GLP-1 agonists and related formulations were well-known .............. 23
`Parenteral dosage forms for peptide-based drugs .............................. 23
`1.
`Tonicity and osmolarity of the parenteral formulation ............ 25
`2.
`pH and buffering capacity of the parenteral formulation ........ 26
`3.
`Avoiding particulates in the parenteral formulation ................ 27
`4.
`Vehicles and diluents of the parenteral formulation ................ 27
`5.
`Excipients of the parenteral formulation ................................. 28
`VIII. Scope and Content of the Prior Art .............................................................. 29
`A. WO 2011/138421 (“WO ’421”) ......................................................... 30
`B.
`Clinical Trial No. NCT00696657 (NCT657) ..................................... 31
`C. WO 2006/097537 (“WO ’537”) ......................................................... 33
`
`B.
`C.
`D.
`
`i
`
`CONFIDENTIAL
`
`Novo Nordisk Exhibit 2026
`Dr. Reddy's Lab'ys, Inc. v. Novo Nordisk A/S
`IPR2024-00009
`Page 00002
`
`

`

`
`
`IX.
`
`X.
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`Lovshin ............................................................................................... 37
`D.
`U.S. Patent No. 8,114,833 (“’833 patent”) ........................................ 38
`E.
`F. Madsbad 2011 .................................................................................... 39
`G. Other Art That Informs the POSA’s Knowledge ............................... 40
`1.
`U.S. Patent No. 6,268,343 (the “Knudsen patent”) ................. 40
`2.
`Victoza label ............................................................................ 42
`3. WO 03/002136 (“WO ’136”)................................................... 42
`4.
`Additional prior art and references .......................................... 44
`5.
`The inventor’s knowledge of the formulation art .................... 45
`Invalidity of the Claims of the ’462 Patent .................................................. 45
`A.
`The State of the Art and a POSA’s Background Knowledge ............ 46
`B.
`Claims 4, 5, and 7 of the ’462 patent would have been obvious
`over WO ’421, NCT657, WO ’537, and/or Lovshin, optionally
`in view of one or more of the ’833 Patent and Madsbad, in view
`of the knowledge of a POSA .............................................................. 53
`1.
`The dependent limitations of claim 4 would have been
`obvious ..................................................................................... 54
`The dependent limitations of claim 5 would have been
`obvious ..................................................................................... 59
`The dependent limitations of claim 7 would have been
`obvious ..................................................................................... 62
`Conclusion ............................................................................... 64
`4.
`Claims 4, 5, and 7 of the ’462 patent would have been obvious
`over WO ’421 alone or in view of the ’833 patent ............................ 65
`Claims 4, 5, and 7 of the ’462 patent would have been obvious
`over WO ’537 considering Lovshin ................................................... 68
`Reservation of Rights ................................................................................... 69
`
`C.
`
`D.
`
`2.
`
`3.
`
`ii
`
`CONFIDENTIAL
`
`Novo Nordisk Exhibit 2026
`Dr. Reddy's Lab'ys, Inc. v. Novo Nordisk A/S
`IPR2024-00009
`Page 00003
`
`

`

`
`
`
`
`
`TABLE OF ABBREVIATIONS
`
`Abbreviation
`Full Name of Cited Reference
`’366 patent
`U.S. Patent No. 5,164,366
`’462 patent
`U.S. Patent No. 10,335,462
`’674 patent
`U.S. Patent No. 7,022,674
`’727 patent
`U.S. Patent No. 6,284,727
`’833 patent
`U.S. Patent No. 8,114,833
`’924 patent
`U.S. Patent No. 6,458,924
`Deposition of Christine Jensen, M.D., Ph.D. (Nov. 8, 2023) Jensen Dep.
`Knudsen 2004
`Knudsen, Glucagon-Like Peptide-1: The Basis of a New
`Class of Treatment for Type 2 Diabetes, 47 J. MED. CHEM.
`4128 (2004)
`U.S. Patent No. 6,268,343
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus, 5 NATURE REVIEWS ENDOCRINOLOGY 262 (2009)
`Lund, Emerging GLP-1 Receptor Agonists, 16 EXPERT
`OPINION ON EMERGING DRUGS 607 (2011)
`Madsbad et al., An Overview of Once-Weekly Glucagon-
`Like Peptide-1 Receptor Agonists—Available Efficacy and
`Safety Data and Perspectives
`for
`the Future, 13
`DIABETES, OBESITY & METABOLISM, 394 (2011)
`Boylan, Parenteral Products, in MODERN PHARMACEUTICS
`(Gilbert S. Banker et al. eds., 3d ed. 1996)
`Clinical Trial No. NCT00696657
`Ozempic prescribing information (Oct. 2022)
`REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY
`(Alfonso R. Gennaro ed., 20th ed. 2000)
`Victoza, PHYSICIANS’ DESK REFERENCE (65th ed. 2010)
`WO 00/37098
`WO 03/002136
`WO 2011/058193
`
`Knudsen patent
`Lovshin
`
`Lund
`
`Madsbad 2011
`
`Modern Pharmaceutics
`
`NCT657
`Ozempic label
`Remington
`
`Victoza label
`WO ’098
`WO ’136
`WO ’193
`
`iii
`
`CONFIDENTIAL
`
`Novo Nordisk Exhibit 2026
`Dr. Reddy's Lab'ys, Inc. v. Novo Nordisk A/S
`IPR2024-00009
`Page 00004
`
`

`

`
`
`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`WO 2011/073328
`WO 2011/138421
`WO 2006/097537
`
`Abbreviation
`WO ’328
`WO ’421
`WO ’537
`
`4
`
`CONFIDENTIAL
`
`Novo Nordisk Exhibit 2026
`Dr. Reddy's Lab'ys, Inc. v. Novo Nordisk A/S
`IPR2024-00009
`Page 00005
`
`

`

`
`
`
`1. My name is Paul Dalby, Ph.D. I have been retained by Dr. Reddy’s
`
`Laboratories, Ltd. and Dr. Reddy’s Laboratories,
`
`Inc.
`
`(“DRL”), Rio
`
`Biopharmaceuticals Inc. and EMS S/A (collectively “Rio”), Sun Pharmaceutical
`
`Industries Ltd. and Sun Pharmaceutical Industries, Inc. (collectively “Sun”), Zydus
`
`Worldwide DMCC, Zydus Pharmaceuticals (USA) Inc., and Zydus Lifesciences
`
`Limited, (collectively “Zydus”), and Mylan Pharmaceuticals Inc. (“MPI”)
`
`(collectively, “Defendants”). Defendants have asked me to provide my expert
`
`opinions regarding the invalidity of claims 4, 5, and 7 of U.S. Patent No. 10,335,462
`
`(“’462 patent”). I understand Novo Nordisk, Inc. and Novo Nordisk A/S
`
`(collectively, “Plaintiffs” or “Novo”) assert that Defendants infringe claims 1, 3, 4,
`
`5, and 7 of the ’462 patent (“the asserted claims”). Because claims 1 and 3 of the
`
`’462 patent relate only to subject matter outside my area of expertise, I have not been
`
`asked to opine on those claims. I therefore address only claims 4, 5, and 7 of the
`
`’462 patent, which relate to my technical area of expertise. I reserve the right to
`
`address the invalidity of any additional claims later asserted by Plaintiffs.
`
`I.
`
`QUALIFICATIONS AND BACKGROUND
`
`A. Education and Experience; Prior Testimony
`
`2.
`
`I earned my doctorate at Cambridge University, UK, in 1998 where I
`
`studied protein folding mechanisms, using protein engineering to alter the relative
`
`stabilities of the native, denatured, intermediate and transition states, and evaluating
`
`1
`
`CONFIDENTIAL
`
`Novo Nordisk Exhibit 2026
`Dr. Reddy's Lab'ys, Inc. v. Novo Nordisk A/S
`IPR2024-00009
`Page 00006
`
`

`

`
`
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`
`
`
`I declare that all statements made herein of my knowledge are true, and that
`
`all statements made on information and belief are believed to be true, and that these
`
`statements were made with the knowledge that willful false statements and the like
`
`so made are punishable by fine or imprisonment, or both, under Section 1001 of Title
`
`18 of the United States Code.
`
`Dated: March 19, 2024
`
`By:
`
`Dr. Paul Dalby
`
`
`
`70
`
`CONFIDENTIAL
`
`Novo Nordisk Exhibit 2026
`Dr. Reddy's Lab'ys, Inc. v. Novo Nordisk A/S
`IPR2024-00009
`Page 00007
`
`