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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 CHRISTOPHER A. VELLTURO,
`Ph.D. IN SUPPORT OF PATENT OWNER’S RESPONSE TO
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT No. 10,335,462
`
`PROTECTIVE ORDER MATERIAL
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`I. OVERVIEW AND SUMMARY ...................................................................... 1
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`A. QUALIFICATIONS AND EXPERIENCE .................................................................. 1
`B. ASSIGNMENT .................................................................................................... 2
`C. MATERIALS CONSIDERED ................................................................................. 3
`D. SUMMARY OF CONCLUSIONS ............................................................................ 3
`
`II. BACKGROUND ............................................................................................... 7
`
`A. DIABETES .......................................................................................................... 7
`B. OVERVIEW OF DRUGS USED TO TREAT TYPE 2 DIABETES ................................ 9
`1. Attributes Driving Demand for Prescription Type 2 Diabetes Drugs ....... 15
`2. Supply of Prescription Type 2 Diabetes Drugs .......................................... 24
`3. Background Summary ................................................................................ 58
`
`III. COMMERCIAL SUCCESS OF OZEMPIC® .......................................... 59
`
`A. COMMERCIAL SUCCESS AND NEXUS – GENERAL CONSIDERATIONS ............... 59
`B. COMMERCIAL SUCCESS OF OZEMPIC® ............................................................ 61
`1. Dollar Sales ................................................................................................ 61
`2. Prescriptions .............................................................................................. 65
`C. NEXUS BETWEEN OZEMPIC®’S SUCCESS AND THE ’462 PATENTED INVENTIONS
`
`67
`1. The ’462 Patented Inventions as Used in Ozempic®.................................. 68
`2. Ozempic® Dollar Sales and Prescriptions Embodying the ’462 Patented
`Inventions .......................................................................................................... 69
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`3. Physician Satisfaction with Ozempic® is Related to Benefits Conferred by
`the ’462 Patented Inventions ............................................................................. 75
`4. Ozempic® Promotional Materials Focus Substantially on Benefits that I
`Understand are Made Possible by the ’462 Patented Inventions ..................... 78
`5. Promotional Efforts Relating to Ozempic® Are
` Those
`Undertaken Generally Among Type 2 Diabetes Drugs .................................... 84
`6. Ozempic®’s Success Is Not Driven by the Success of Prior Novo Nordisk
`Type 2 Diabetes Products ................................................................................. 87
`7. Ozempic®’s Pricing is
` Competitor Type 2 Diabetes Drugs
`90
`
`8. The Economic Incentives to Develop the ’462 Patented Inventions Are Not
`Substantially Diminished by the Presence of a Blocking Patent ...................... 92
`D. CONCLUSION ................................................................................................... 95
`
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`I, Christopher A. Vellturo, Ph.D., hereby declare under penalty of perjury:
`
`I. OVERVIEW AND SUMMARY
`
`A. Qualifications and Experience
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`1. I am the founder and president of Quantitative Economic Solutions, LLC, a
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`microeconomic consulting firm. I received a Doctor of Philosophy degree (Ph.D.)
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`in Economics from the Massachusetts Institute of Technology in Cambridge,
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`Massachusetts in 1989. My fields of specialization include industrial organization
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`and econometrics. My curriculum vitae, which lists my testimony for the last four
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`years and my publications, is attached as Appendix A. Except as otherwise
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`indicated, I have personal knowledge of the facts set forth in this Declaration. All
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`statements herein made of my own knowledge are true and all statements made on
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`information and belief are believed to be true. If called upon to do so, I would
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`testify competently thereto.
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`2. I have evaluated pharmaceutical patent issues in the context of commercial success
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`and injunctive relief considerations on numerous occasions. I also have extensive
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`experience in the valuation of intellectual property and in the assessment of
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`economic injury/damages sustained as a result of patent, copyright, and/or
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`trademark infringement. Industries that I have studied in this context include:
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`pharmaceutical products, over-the-counter medications and instruments, medical
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`devices, consumer products, computer hardware and software, and semiconductors.
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`I have been qualified and have testified as an expert in many federal courts
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`throughout the United States and before the U.S. Patent Trial and Appeal Board
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`(“PTAB”) as an economist generally, as an expert in statistics/surveys, and as an
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`expert in the economics of the pharmaceutical industry specifically.
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`B. Assignment
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`3. As part of my current assignment, I have been asked by Groombridge, Wu,
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`Baughman and Stone LLP, counsel for Novo Nordisk (or “Patent Owner”), to
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`evaluate the commercial success of the drug Ozempic® and the extent to which
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`Ozempic®’s commercial success is causally linked to the claims-at-issue from U.S.
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`Patent No. 10,335,462 (“the ’462 patent”), which I understand covers methods of
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`treating type 2 diabetes (“T2D”) using semaglutide 1.0 mg once weekly. I refer to
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`the inventions covered by the ’462 patent as the “’462 Patented Inventions.” I have
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`also been asked to evaluate the extent to which the presence of U.S. Patent Nos.
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`8,129,343 (“the ’343 patent”) and 8,536,122 (“the ’122 patent”) may have acted as
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`so-called “blocking” patents that would have dampened the marketplace incentives
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`for third parties to undertake efforts to pursue and develop the inventions claimed
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`by the ’462 patent. Additionally, I understand from counsel that I may not have the
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`opportunity to submit a reply or otherwise respond to arguments that Petitioners
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`may submit regarding commercial success.
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`C. Materials Considered
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`4. In connection with this matter, I have considered information from the following
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`sources:
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`(cid:120) publicly available information;
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`(cid:120) materials and data supplied by Patent Owner; and
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`(cid:120) the expert declaration of Dr. Robin S. Goland.1
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`5. A complete list of the information I cited in forming my opinions can be found in
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`Appendix B to this declaration. The information I relied on to form my ultimate
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`conclusions are cited in this declaration and the attached appendices.2, 3
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`D. Summary of Conclusions
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`6. Based on my training and experience, the information I have reviewed, and the
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`analyses I have performed, at a summary level I have reached the following
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`conclusions.
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`
`1 Exhibit 2054 (Expert Declaration of Robin S. Goland, M.D. In Support of Patent
`Owner’s Response to Petition for Inter Partes Review of U.S. Patent No. 10,335,462
`(IPR2023-00724), January 16, 2024 (“Goland Declaration”)).
`2 If called on to testify, I may rely upon demonstrative aids (e.g., charts or graphs)
`summarizing the data presented or referred to in this declaration.
`3 QES is being compensated for my time spent on this matter at an hourly rate of
`$1,100, which is my customary rate. QES is also being compensated for the time spent
`on this matter by persons working at my direction. Their rates are lower than my hourly
`rate. Payment is not contingent on the opinions I render or the outcome of this matter.
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`7. I find that Ozempic® has achieved considerable marketplace success and that this
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`success is, to a significant degree, attributable to the ’462 Patented Inventions:
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`(cid:120) With regard to Ozempic®’s marketplace success:
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`o Ozempic® has attained and maintained considerable marketplace success
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`since its introduction in 2018;
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`o Ozempic® has generated more than $19.3 billion in U.S. net dollar sales
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`since its launch in 2018 through September 2023, with net sales increasing in
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`each full calendar year since launch;
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`o Ozempic® achieved “blockbuster” drug status (i.e., having more than $1
`
`billion in annual net sales in the United States) in 2019, its first full year of
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`sales after launch, and has maintained this status in each year from 2019 to
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`2023;
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`o Ozempic® has attained substantial volumes of dollar sales and prescriptions
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`among the newer classes of non-insulin anti-diabetic treatments;
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`o Ozempic® has increased its shares of both sales and prescriptions every year
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`among modern non-insulin anti-diabetic treatments despite launching into a
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`crowded and growing treatment landscape that has seen additional product
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`launches.
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`(cid:120) With regard to the extent to which Ozempic®’s commercial success is
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`attributable to the benefits afforded by the ’462 Patented Inventions:
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`o I understand from counsel that in the context of a Commercial Success
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`inquiry, when the marketed product is an embodiment of the claims and is
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`coextensive with them, there is a presumption of nexus; I further understand
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`from Dr. Robin S. Goland that the use of 1.0 mg of Ozempic® weekly to treat
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`type 2 diabetes embodies the challenged claims of the ’462 patent and is an
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`essential part of the product as prescribed;
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`o A presumption of nexus notwithstanding, I find that the ’462 Patented
`
`Inventions meaningfully contributed to Novo Nordisk’s ability to
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`commercialize Ozempic® and thus to its observed marketplace success.
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`(cid:131) Surveys of physicians who treat type 2 diabetes indicate that the
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`benefits afforded by the ’462 Patented Inventions significantly
`
`contributed to physician decisions to prescribe Ozempic®.
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`(cid:131) Novo Nordisk’s marketing initiatives for Ozempic® have focused on
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`attributes of Ozempic® I understand are attributable to the ’462
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`Patented Inventions, such as its efficacy in treating type 2 diabetes
`
`and once-weekly administration – messaging that resonated and
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`impacted physicians’ prescribing behavior;
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`(cid:131) Ozempic®’s prescription and sales data do not indicate any
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`significant off-label usage, let alone off-label usage that could have
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`been significant enough to substantially diminish the nexus between
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`the ’462 Patented Inventions and the profound marketplace success
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`demonstrated by overall Ozempic® 1.0 mg prescriptions and sales.
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`(cid:120) Relatedly, I find that Ozempic®’s commercial success is not due to:
`
`o Inordinate marketing and promotional activity relative to the other branded
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`therapies in the type 2 diabetes treatment category;
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`o Aggressively low pricing or excessive discounting and rebates relative to
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`competitor type 2 diabetes treatments; or,
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`o the success of previous Novo Nordisk type 2 diabetes treatments.
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`8. Finally, I assess whether the presence of the ’343 patent or ’122 patent may have
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`acted as so-called “blocking” patents that would have significantly dampened the
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`marketplace incentives for third parties to undertake efforts to pursue and develop
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`the ’462 Patented Inventions. Here, I find that the existence of the ’343 and ’122
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`patents did not substantially diminish the incentives to develop the ’462 Patented
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`Inventions.
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`9. This declaration and the opinions expressed herein are based on my analysis of the
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`information I have considered to date. I may supplement, refine, or revise my
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`analysis as appropriate if additional testimony, documents, or other discovery
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`materials become available, including, without limitation, other expert declarations
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`(subject to the expert discovery schedule set forth by the PTAB).
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`II.BACKGROUND
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`10. In this section, I provide general background information regarding type 2 diabetes
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`and the drugs approved to treat type 2 diabetes in the United States. I then discuss
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`factors affecting the demand for and supply of type 2 diabetes drugs, and in
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`particular the prescription type 2 diabetes drugs that I understand have been
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`identified by Novo Nordisk as competitors to Ozempic®.
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`11. My presentation and consideration of technical information is based upon my
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`understanding as provided to me by Dr. Robin S. Goland,4 and upon my review of
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`materials produced in this matter and materials publicly available.
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`A. Diabetes
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`12. Diabetes mellitus (“diabetes”) refers to a group of diseases that occur when the
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`body’s blood glucose (also called blood sugar) – the body’s main source of energy
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`– is too high.5 Prolonged elevated levels of glucose in the bloodstream (known as
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`4 Exhibit 2054 (Goland Declaration).
`5 Exhibit 2351 (https://www.niddk.nih.gov/health-information/diabetes/overview/what-
`is-diabetes), p. 1; Exhibit 2352 (https://www.mayoclinic.org/diseases-
`conditions/diabetes/symptoms-causes/syc-20371444), p. 1.
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`hyperglycemia6) can lead to damage to the heart, blood vessels, eyes, kidneys, and
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`nerves.7 The cause of excessive blood glucose differs among the two primary types
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`of diabetes, type 1 and type 2,8 but in both cases is related to the body’s inability to
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`produce or utilize insulin, a hormone made by the pancreas that helps the body use
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`glucose for energy and regulate blood glucose levels.9 In its 2020 National
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`Diabetes Statistics Report, the U.S. Centers for Disease Control and Prevention
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`(“CDC”) stated that approximately 10.5 percent of the U.S. population (34.2
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`million people) has diabetes.10
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`13. Type 2 diabetes is the more common form of diabetes.11 Type 2 diabetes can
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`develop at any age, but it is most common in middle-aged and older people.12 The
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`
`6 Exhibit 2353 (https://www.mayoclinic.org/diseases-
`conditions/hyperglycemia/symptoms-causes/syc-20373631), p. 1.
`7 Exhibit 2353 (https://www.mayoclinic.org/diseases-
`conditions/hyperglycemia/symptoms-causes/syc-20373631), pp. 1-3.
`8 Exhibit 2352 (https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-
`causes/syc-20371444), p. 1. In addition to type 1 and type 2 diabetes, gestational
`diabetes occurs in pregnant women whose bodies are not able to produce or use the
`insulin required for the pregnancy. See Exhibit 2354
`(https://www.cdc.gov/diabetes/basics/gestational.html), p. 1.
`9 Exhibit 2351 (https://www.niddk.nih.gov/health-information/diabetes/overview/what-
`is-diabetes), p. 1; Exhibit 2355 (https://www.niddk.nih.gov/Dictionary/I/insulin), p. 1.
`10 I note that this estimate is based upon 2016 statistics and survey results (see Exhibit
`2356 (https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-
`report.pdf), p. 4).
`11 Exhibit 2351 (https://www.niddk.nih.gov/health-information/diabetes/overview/what-
`is-diabetes), p. 2.
`12 Exhibit 2357 (https://www.niddk.nih.gov/health-information/diabetes/overview/what-
`is-diabetes/type-2-diabetes), pp. 1-2.
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`CDC estimated that approximately 90 to 95 percent of the total U.S. population
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`with diabetes has type 2 diabetes, equaling roughly 30.8 million to 32.5 million
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`people.13 The CDC further estimated that type 2 diabetes affects roughly 9.5
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`percent to 10 percent of the overall U.S. population.14
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`B. Overview of Drugs Used to Treat Type 2 Diabetes15
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`14. As Ozempic® is indicated for the treatment of type 2 diabetes,16 I focus my
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`discussion of the factors affecting demand for and supply of diabetes drugs on
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`those used to treat type 2 diabetes in particular.
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`15. In addition to lifestyle choices (e.g., healthy eating and physical exercise), weight
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`loss, regular monitoring of blood glucose levels, and insulin therapy (i.e., the direct
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`injection of insulin into the body), prescription non-insulin anti-diabetic drugs are
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`13 34.2 million Americans * 90 percent = 30.8 million Americans; 34.2 million
`Americans * 95 percent = 32.5 million Americans (see Exhibit 2356
`(https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-
`report.pdf), pp. 3-4).
`14 10.5 percent of the U.S. population with diabetes * 90 percent type 2 diabetes = 9.45
`percent; 10.5 percent of the U.S. population with diabetes * 95 percent type 2 diabetes =
`9.98 percent (see Exhibit 2356
`(https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-
`report.pdf), pp. 3-4).
`15 In this section, I exclude drugs that have insignificant sales and/or have been
`discontinued due to safety/tolerability reasons, i.e., Juvisync® and Qternmet XR®.
`16 Exhibit 2069
`(https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209637s020s021lbl.pdf),
`p. 1.
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`often used to help people with diabetes to control their blood glucose levels.17 A
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`number of classes of non-insulin anti-diabetic drugs are used to treat type 2
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`diabetes. I provide a brief overview of the main classes of these drugs in the
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`following paragraphs.
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`16. Sulfonylureas, the first class of non-insulin anti-diabetic drug introduced in the
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`United States for the treatment of type 2 diabetes,18 help the body secrete more
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`insulin.19 Sulfonylureas are safe, inexpensive, and predictable, but the incidence of
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`hypoglycemia (a condition in which a patient’s blood sugar is below normal levels)
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`limits their use.20 Second-generation sulfonylureas (i.e., glyburide and glipizide)
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`were first introduced in the United States in 1984 as the branded products DiaBeta®
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`(glyburide), Micronase® (glyburide), and Glucotrol® (glipizide).21 A third-
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`17 Exhibit 2358 (https://www.mayoclinic.org/diseases-conditions/type-2-
`diabetes/diagnoss-treatment/drc-20351199), pp. 1-3.
`18 Exhibit 2359 (https://www.medscape.com/viewarticle/722513_3), p. 3; Exhibit 2360
`(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/), p. 1.
`19 Exhibit 2358 (https://www.mayoclinic.org/diseases-conditions/type-2-
`diabetes/diagnosis-treatment/drc-20351199), pp. 2-3.
`20 Exhibit 2360 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/), p. 1;
`Exhibit 2361 (https://www.niddk.nih.gov/health-
`information/diabetes/overview/preventing-problems/low-blood-glucose-
`hypoglycemia,1), pp. 3-4.
`21 Exhibit 2360 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/), pp. 1, 3;
`Exhibit 2362
`(http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&va
`rApplNo=017532), p. 1; Exhibit 2363
`(http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&va
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`generation sulfonylurea, glimepiride, was first introduced in the United States in
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`1995 as the branded product Amaryl®.22
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`17. Biguanides increase the sensitivity of the body’s tissues to insulin and lower
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`glucose production in the liver.23 One such biguanide medication is metformin.24
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`Metformin is often prescribed for type 2 diabetes but may not lower blood sugar
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`enough on its own, requiring lifestyle changes such as weight loss and increased
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`physical activity.25, 26 Metformin was first introduced in the United States in 1995
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`as the branded product Glucophage®.27
`
`
`rApplNo=017498), p. 1; Exhibit 2364
`(http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&va
`rApplNo=017783), p. 1.
`22 Exhibit 2360 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/), pp. 1, 3;
`Exhibit 2365
`(https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&v
`arApplNo=020496), p. 1.
`23 Exhibit 2366 (https://my.clevelandclinic.org/health/treatments/25004-biguanides), pp.
`3-4.
`24 Exhibit 2367 (https://pubmed.ncbi.nlm.nih.gov/7862618/), p. 1.
`25 Exhibit 2368 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138587/), pp. 2-5.
`26 Exhibit 2358 (https://www.mayoclinic.org/diseases-conditions/type-2-
`diabetes/diagnosis-treatment/drc-20351199), p. 2.
`27 Exhibit 2360 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/), p. 1;
`Exhibit 2369
`(http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&va
`rApplNo=020357), p. 1.
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`18. Meglitinides, like sulfonylureas, stimulate the pancreas to secrete more insulin.28
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`Meglitinides are faster acting than sulfonylureas but have a shorter-lasting effect.29
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`Meglitinides were first introduced in the United States in 1997 with the approval of
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`the branded product Prandin® (repaglinide).30
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`19. Thiazolidinediones make the body’s tissues more sensitive to insulin.31 These
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`medications have been linked to weight gain, increased risk of heart failure, and
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`other serious side effects and are therefore not recommended as a first-choice
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`treatment.32 The first thiazolidinedione was introduced in the United States in
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`1997, though it was withdrawn in 2000 after it was found to cause liver damage.33
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`28 Exhibit 2370 (https://diabetesjournals.org/spectrum/article/27/2/82/32029/A-Brief-
`History-of-the-Development-of-Diabetes), p. 3.
`29 Exhibit 2370 (https://diabetesjournals.org/spectrum/article/27/2/82/32029/A-Brief-
`History-of-the-Development-of-Diabetes), p. 3.
`30 Exhibit 2370 (https://diabetesjournals.org/spectrum/article/27/2/82/32029/A-Brief-
`History-of-the-Development-of-Diabetes), p. 3; Exhibit 2371
`(http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&va
`rApplNo=020741), p. 1.
`31 Exhibit 2358 (https://www.mayoclinic.org/diseases-conditions/type-2-
`diabetes/diagnosis-treatment/drc-20351199), p. 3.
`32 Exhibit 2358 (https://www.mayoclinic.org/diseases-conditions/type-2-
`diabetes/diagnosis-treatment/drc-20351199), p. 3; Exhibit 2372
`(https://www.ncbi.nlm.nih.gov/books/NBK551656/), pp. 2-4.
`33 Exhibit 2360 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/), p. 2.
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`
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`Two additional thiazolidinediones – Actos® (pioglitazone) and Avandia®
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`(rosiglitazone) – were approved in 1999.34
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`20. Glucagon-like peptide-1 (“GLP-1”) receptor agonists (including Ozempic®) imitate
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`the action of the naturally-occurring GLP-1 hormone in binding to GLP receptor
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`proteins, which then triggers the release of insulin from the pancreas.35 GLP-1
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`receptor agonists have other effects beyond the release of insulin, including
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`inhibiting gastric emptying, delaying absorption of food, and regulating appetite
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`and food intake.36 GLP-1 receptor agonists were first introduced in the United
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`States in 2005, with the launch of Byetta® (exenatide).37
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`21. Dipeptidyl peptidase-4 (“DPP-4”) inhibitors counteract the action of the DPP-4
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`enzyme, which breaks down GLP-1, thereby increasing the level of GLP-1 in the
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`bloodstream and stimulating the secretion of insulin.38 DPP-4 inhibitors are not
`
`
`34 Exhibit 2360 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714066/), p. 2;
`Exhibit 2485
`(http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&va
`rApplNo=021073), p. 1; Exhibit 2486
`(http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&va
`rApplNo=021071), p. 1.
`35 Exhibit 2368 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138587/), pp. 5-6;
`Exhibit 2373 (https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists),
`pp. 3-4.
`36 Exhibit 2368 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138587/), p. 5.
`37 Exhibit 2374 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536194/), p. 3.
`38 Exhibit 2368 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138587/), p. 8.
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`able to raise GLP-1 levels to the same extent as GLP-1 agonists, however.39 DPP-4
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`inhibitors were first introduced in the United States in 2006, with the launch of
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`Januvia® (sitagliptin).40
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`22. Sodium glucose co-transporter-2 (“SGLT2”) inhibitors prevent reabsorption of
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`glucose in renal tissue.41 Excess blood sugar is then excreted in urine.42 SGLT2
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`inhibitors were first introduced in the United States in 2013 with the approval of
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`Invokana® (canagliflozin).43
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`23. I focus my subsequent analyses on the newer classes of non-insulin type 2 diabetes
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`drugs that
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` competing most directly with Ozempic® –
`
`namely, GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors – often
`
`collectively referred to as MNIADs (modern non-insulin anti-diabetics)
`
`
`
`.44
`
`
`39 Exhibit 2368 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138587/), p. 8.
`40 Exhibit 2370 (https://diabetesjournals.org/spectrum/article/27/2/82/32029/A-Brief-
`History-of-the-Development-of-Diabetes), p. 3; Exhibit 2375
`(https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2006/021995s000ltr.pdf), p.
`1.
`41 Exhibit 2376 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269649/), p. 3.
`42 Exhibit 2376 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269649/), p. 3.
`43 Exhibit 2377 (https://www.prnewswire.com/news-releases/us-fda-approves-invokana-
`canagliflozin-for-the-treatment-of-adults-with-type-2-diabetes-200638361.html), p. 1.
`44 See, e.g., Appendix C; Exhibit 2301, worksheet “NOTES”. See also,
`
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`
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`1. Attributes Driving Demand for Prescription Type 2 Diabetes Drugs
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`24. In this section, I discuss the key attributes of prescription type 2 diabetes drugs that
`
`can drive demand for these drugs – namely, efficacy, safety, convenience, patient
`
`adherence, and cost. Physicians are the central decision-makers in prescription
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`choices relating to treating type 2 diabetes, and the demand for type 2 diabetes
`
`drugs is strongly driven by physician preference, though consideration is also given
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`to patient preferences and individualized needs.45 My understanding is based on
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`publicly available information and literature, internal Novo Nordisk documents,
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`and declarations of other experts testifying in this matter.
`
`
`(NN-OZEM-003735283), p. 9);
`
`
`
` (Exhibit 2314 (NN-OZEM-004656390), pp. 3-4);
`
`
`
` (Exhibit 2330
`(NN-OZEM-004723593), pp. 8-13; see also Exhibit 2325 (NN-OZEM-004691302), pp.
`8-9; Exhibit 2333 (NN-OZEM-004741982), pp. 14-15);
`
`
` (see, e.g., Exhibit 2312 (NN-OZEM-004063922), worksheet “1 Non-
`Insulin Performance).
`45 Exhibit 2378 (http://www.diabetes.org/living-with-diabetes/treatment-and-care)
`(noting that “every individual [patient] needs unique care”), p. 1.
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`25.
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`26.
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`
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`a. Efficacy
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`
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`.46 As discussed
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`previously, diabetes is caused by high blood glucose levels. Physicians monitor
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`patients’ blood glucose principally by measuring hemoglobin A1c (“HbA1c” or
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`“A1c,” also referred to as “A1C”).47 The A1c test, which is performed at the
`
`direction of a physician, provides a unique measure that correlates with a patient’s
`
`mean plasma glucose concentration over a period of 2-3 months, providing insight
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`into how well the patient’s blood sugar has been controlled over time and how well
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`the patient’s diabetes care plan is working.48
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`
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`
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`46 See, e.g., Exhibit 2321 (NN-OZEM-004684467), pp. 24-25; Exhibit 2325 (NN-
`OZEM-004691302), pp. 31-32; Exhibit 2054 (Goland Declaration), ¶¶ 45, 47, 60, 93.
`47 Exhibit 2379 (https://www.mynovoinsulin.com/diabetes-education/managing-
`diabetes.html), p. 4.
`48 Exhibit 2380 (https://www.mayoclinic.org/tests-procedures/a1c-test/about/pac-
`20384643), p. 1; Exhibit 2379 (https://www.mynovoinsulin.com/diabetes-
`education/managing-diabetes.html), p. 4.
`49 See, e.g., Exhibit 2316 (NN-OZEM-004679316), pp. 108-112; Exhibit 2330 (NN-
`OZEM-004723593), pp. 28-29; Exhibit 2327 (NN-OZEM-004701779), pp. 52-53;
`Exhibit 2326 (NN-OZEM-004691816), pp. 14-15; Exhibit 2325 (NN-OZEM-
`004691302), pp. 27-28; Exhibit 2321 (NN-OZEM-004684467), pp. 24-25.
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`understand from Dr. Goland that she has at times changed her approach to treating
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`type 2 diabetes partly in response to new evidence on the efficacy attributes of type
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`.50 Indeed, I
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`2 diabetes drugs, such as A1C reduction.51
`
`
`
`
`
`
`
`
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`52
`
`27. Type 2 diabetes is a progressive illness, and timely treatment escalation therefore
`
`plays an important role in efficaciously treating the disease.53 Historically,
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`intensifying treatment was challenging due to the adverse effects of insulin-based
`
`treatments (such as hypoglycemia and weight gain).54 Newer treatments can be
`
`added or intensified without the same risks of hypoglycemia as insulin.55 It is
`
`common for physicians to recommend dose escalation (“increase from a lower
`
`initial dose to a higher end dose to maximize treatment benefit”) in type 2 diabetes
`
`
`50 Exhibit 2306 (NN-OZEM-003732069), pp. 6-7; Exhibit 2307 (NN-OZEM-
`003732120), pp. 29-34.
`51 Exhibit 2054 (Goland Declaration), ¶¶ 47, 61-78, 81-83.
`52 Exhibit 2311 (NN-OZEM-004055726), pp. 5-8.
`53 Exhibit 2381 (https://link.springer.com/article/10.1007/s13300-017-0287-y), p. 2;
`Exhibit 2054 (Goland Declaration), ¶¶ 29, 35, 47.
`54 Exhibit 2381 (https://link.springer.com/article/10.1007/s13300-017-0287-y), p. 3.
`55 Exhibit 2381 (https://link.springer.com/article/10.1007/s13300-017-0287-y), p. 3.
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`treatment.56 According to a survey of physicians published in 2023, the top three
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`reasons for recommending dose escalation were: “the need for better glycemic
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`control,” “ability to decrease the total number of medications,” and “the need for
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`the patient to lose weight.”57
`
`28. With the growth in available type 2 diabetes treatment options, physicians have
`
`begun to consider additional therapeutic effects in their prescribing decisions.58
`
`Some of these additional therapeutic effects, such as weight loss, can help patients
`
`control their type 2 diabetes, as “when [one] weigh[s] less, [the] pancreas is better
`
`able to keep up with [the] body’s need for insulin,”59 and patients who experience
`
`weight loss “show[] sustained enhanced insulin sensitivity.”60 Additionally, one
`
`study found that “in established T2DM [(type 2 diabetes mellitus)] weight loss has
`
`been shown to improve glycaemic control”61 while another found that “[p]eople
`
`who lose at least 10% of their body weight in the first year a