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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`————————————————
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`MYLAN PHARMACEUTICALS INC.
`and PFIZER INC.,
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`Petitioners,
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`v.
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`SANOFI-AVENTIS DEUTSCHLAND GMBH,
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`Patent Owner.
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`————————————————
`Case No. IPR2018-01670 - Patent No. 8,679,069
`Case No. IPR2018-01678 - Patent No. 8,992,486
`Case No. IPR2018-01680 - Patent No. 9,526,844
`Case No. IPR2018-01682 - Patent No. 9,526,844
`Case No. IPR2018-01684 - Patent No. 9,604,008
`Case No. IPR2019-00122 - Patent No. 8,992,486
`————————————————
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`DECLARATION OF DR. WILLIAM C. BIGGS
`IN SUPPORT OF MYLAN-PFIZER REPLY
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`I.
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`INTRODUCTION
`1. My name is Dr. William Curtis Biggs. I am a Medical Doctor
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`specializing in the treatment of metabolic diseases, and have extensive experience
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`treating patients with diabetes.
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`2.
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`Counsel for Mylan Pharmaceuticals, Inc. (“Mylan”) and Pfizer Inc
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`(“Pfizer”) approached me for expert assistance in inter partes review of involved U.S.
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`Patent Nos. 8,679,069 (EX1001), 8,992,486 (EX1003), 9,526,844 (EX1004), and
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`9,604,008 (EX1005). Specifically, Mylan and Pfizer requested my views on
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`considerations in prescribing insulin for patients.
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`A. Education and Experience
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`3.
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`I received my bachelor’s degree in chemistry from the University of
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`California, San Diego (magna cum laude) in 1978. I then attended medical
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`school at the University of Texas, Southwestern Medical School at Dallas, and
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`graduated in 1982 with a medical doctorate degree. I have been Board Certified
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`by the American Board of Internal Medicine in Internal Medicine since 1985, and
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`by the American Board of Preventative Medicine in Clinical Informatics in 2014.
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`4.
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`I have extensive post-doctoral experience, starting as an Intern in
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`Medicine at the University of California, San Diego from 1982-83. I served as a
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`Junior Assistant Resident at the New England Deaconess Hospital in Boston from
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`1983-84, and then as a Senior Assistant Resident from 1984-85. From 1985-86, I was
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`a Fellow in Endocrinology/Diabetes at the Joslin Diabetes Center, Harvard Medical
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`School, and New England Deaconess Hospital in Boston. The Joslin Diabetes Center is
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`the largest diabetes research center and clinic in the world, and a preeminent research
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`institution for endocrinology and metabolic diseases, providing cutting-edge care for
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`patients afflicted with diabetes.
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`5.
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`I currently hold academic and clinical appointments in Amarillo, Texas,
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`including as a Clinical Assistant Professor in the Department of Internal Medicine at
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`Texas Tech School of Medicine in Amarillo. I am the Medical Director of the
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`Diabetes Center at Northwest Texas Hospital in Amarillo, Texas, the only American
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`Diabetes Association recognized education program in our region. I have active staff
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`privileges with the Baptist St. Anthony’s Hospital in Amarillo, Texas for hospital
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`inpatient consultation.
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`6.
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`I am a Founder and Chief Executive Officer of the Amarillo Legacy
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`Medical Accountable Care Organization (ACO) since 2012. As the director of an
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`Accountable Care Organization, I am responsible for ensuring the quality of
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`healthcare delivery under a Medicare Shared Savings Program contract. I supervise
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`300 healthcare providers who are working to improve healthcare delivery, improve
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`patient outcomes, and reduce costs.
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`7.
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`I am the Managing Partner and Chief Medical Information Officer for
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`Amarillo Medical Specialists LLP since 1995. Amarillo Medical Specialists LLP
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`currently manages 43 medical providers in the Amarillo, Texas area.
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`8.
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`I also currently hold committee positions with the American Association
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`of Clinical Endocrinologists and serve as the Current Procedural Terminology (CPT)
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`Advisor representing the American Association of Clinical Endocrinologists (AACE)
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`at the American Medical Association CPT Editorial Panel.
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`9.
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`I am the Vice Chairman of the Amarillo Hospital District, which is a
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`governmental agency with ability to levy taxes, which provides healthcare for
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`impoverished persons living within the City of Amarillo.
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`10.
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`I have held various leadership positions in local and national medical
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`profession organizations, including serving as President of the Texas Chapter of the
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`American Association of Clinical Endocrinologists, as well as serving on the Board of
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`Directors for various diabetes organizations, including the Juvenile Diabetes
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`Foundation in Amarillo, and the Amarillo Chapter of the American Diabetes
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`Association. I also served on the Board of Governors for the Northwest Texas
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`Healthcare System in Amarillo, and the Board of Directors for the Texas Chapter of
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`the American Association for Clinical Endocrinologists.
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`11.
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`I have been recognized for my past work in endocrinology and medicine,
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`including in Who’s Who in Medicine and Healthcare (1998-2008), Who’s Who in
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`America (2001-2008), in Who’s Who in Science and Engineering (2002-2006), as a
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`Fellow of the American College of Endocrinology (2005), as a Promise Honoree from
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`the Juvenile Diabetes Research Foundation (Amarillo, June 2005), and as a Texas
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`Monthly Magazine “SuperDoctor” in Endocrinology (2005-2019).
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`12.
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`I have published articles and delivered oral presentations specifically on
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`diabetes care and prevention throughout the United States, including as a Program
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`Speaker and Co-Director for Texas AACE Diabetes Management for Primary Care
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`Physicians, and an invited speaker at the HIMSS1 National and Texas Annual
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`Meetings.
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`13.
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`I continue to work as the Principal Investigator for numerous clinical
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`research trials involving diabetes for type 1 and type 2 diabetes, including trials that
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`look specifically at the effect of insulins, devices, patient education, and healthcare
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`costs.
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`14. A copy of my curriculum vitae detailing my education and work
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`experience is included as exhibit EX1049 in support of my declaration.
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`1 Healthcare Information and Management Systems Society.
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`B. Scope of Work
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`15. Mylan and Pfizer have retained me as an expert in this matter,
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`specifically regarding my experience as a clinician treating diabetic patients.
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`16. My opinions are directed principally to long-felt, unmet need arguments
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`provided in cases IPR2018-01670, IPR2018-01678, IPR2018-01680, IPR2018-01682,
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`IPR2018-01684, and IPR2019-00122. For simplicity, I provide the same opinion for
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`each of these cases.
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`17.
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`I receive $600 per hour for my time providing services in this case. No
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`part of my compensation depends upon my professional opinions or on the outcome of
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`this case.
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`18.
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`I have been a principal investigator for a clinical trial of Sanofi-Aventis’s
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`high-concentration insulin glargine product, Toujeo. I do not have any affiliation with
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`any named inventor of the involved patents.
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`A. Legal context
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`19.
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`I have been advised that Sanofi has the burden of producing evidence
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`showing long-felt, unmet need. I have been advised that long-felt, unmet need is
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`assessed as of the filing date of the invention. I have been asked to use March 3, 2003
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`as the date of filing (“filing date”) for the purposes of my analysis, based on the
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`earliest filing date that Sanofi claims. My opinions are true for both the filing date and
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`remain true to the present unless I expressly indicate otherwise.
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`20.
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`I have been advised that a purported long-felt need must focus on what
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`the challenged claims actually claim. I have been advised that when practical
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`differences between prior solutions and the claimed invention are insignificant, or
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`when existing measures adequately address the purported problem, no unmet need
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`exists.
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`B. Materials considered and other bases for testimony
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`21.
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`I have reviewed the declaration of Dr. Robin S. Goland, in which she
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`testifies for Sanofi-Aventis Deutschland GmbH (“Sanofi”) regarding long-felt, unmet
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`need. EX10[Goland], 1. I also reviewed the exhibits she cited.
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`22.
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`I have reviewed U.S. Patent Nos. 8,679,069 (EX1001, particularly
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`claim 1), 8,992,486 (EX1003, particularly claims 1-6, 12-18, 20, 23, 26-30, 32, 33, 36,
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`and 38-40), 9,526,844 (EX1004, particularly claims 21-30), and 9,604,008 (EX1005,
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`particularly claims 1, 3, 7, 8, 11, and 17).
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`23. Other documents that I have considered are cited as exhibits in this
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`declaration. I am advised these exhibits will be filed along with my declaration.
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`24. My opinions are based on my education, on my experience, and on other
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`bases such as articles, government data, discussions with patients, and other relevant
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`knowledge. This declaration states my current opinions, which could change if
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`additional information or analyses become available.
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`II.
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`CONSIDERATIONS IN PRESCRIBING INSULIN DELIVERY
`A. Summary of opinions
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`25.
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`Insulin is a prescription medication. Injection force is not a significant
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`consideration when choosing among available injectable insulin products for diabetic
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`patients. Rather, when prescribing insulin, the overwhelming consideration is the
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`insulin itself. Drug manufacturers determine the forms in which they make their
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`insulins available. Hence, for patients and prescribers the choice of insulin determines
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`the range of delivery-form options, not vice versa. EX1045, 527 (“In U.S. medical
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`practice, the choice of insulin pen will be, to a large extent, determined by the choice
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`of insulin, as particular insulins are specific to certain makes of insulin pen.”).
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`26. At the 2003 filing date, in the United States, long-acting (basal) insulin
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`was overwhelmingly delivered using vials and syringes. While injector pens were
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`available and more commonly used in Europe back then, pens generally had not yet
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`caught on in the United States, in part due to the higher cost. EX1046, 57-58;
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`EX1045, 522 (noting costs). As late as 2010, market penetration of pens in the United
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`States remained low. EX1045, 522 (“In contrast, in the United States, only 15% of
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`patients are thought to use insulin pens.) To the extent patients in the United States
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`used pens, they generally prefer reusable pens over disposable pens because reusable
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`pens were (and continue to be) viewed as better made and more reliable. See EX1047.
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`27. Then as now, various insulin-delivery technologies existed and were
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`largely fungible from the perspective of the patient and prescriber. Specifically,
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`Sanofi’s Lantus product was widely available as a vial product well before it was
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`available in a disposable pen. EX2111, ¶20. When Sanofi launched the Lantus pen,
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`free Lantus samples were provided in pens rather than vials, which accelerated patient
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`transition to its pens (in much the same way that Sanofi now provides free samples of
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`its Toujeo products).
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`28. At the 2003 filing date, several competing insulin-delivery technologies
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`existed. Some (like insulin pumps) did not involve syringes or injection pens. For
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`syringes and pens, the key considerations were the type of insulin and the cost.
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`Individual patients might also have concerns about convenience and freedom (for
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`syringes); inability to mix different insulins together for injection and longer injection
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`time (for pens); durability (for disposable pens); sterility (for reusable pens); and
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`reliability, flexibility and environmental impact (for syringes and disposable pens).
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`EX1046, 58, 61, 68; EX1045, 526 (noting delay in completing pen injections). There
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`were also needle-free injector pens, like Injex, for patients who hate needles. Since
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`insulin products were often available in several delivery forms, in my experience,
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`these trade-offs were resolved without switching the prescribed insulin.
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`29. Available pens at the 2003 filing date were already considered “easy-to-
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`use, convenient, and accurate”. EX1046, 57, 62. Patients who were willing and able to
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`inject themselves could do so with appropriate training. See EX1045, 523 (stressing
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`importance of training). In my experience, injection force was never the reason why
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`patients were unwilling or unable to inject themselves. Patients with age, physical or
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`cognitive constraints that would prevent self-injection would not have been aided by
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`the marginal differences in injection force between FDA-approved injector pens. See
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`EX2114, 5 (“In general, differences in the injection force between insulin pens are
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`relatively small.”) EX1045, 528 (same). In such cases, injection would be delegated to
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`a family member or caregiver. In my experience, there was no difference in the level
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`of training for SoloStar and other disposable pens. Reusable pens also had similar
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`training requirements, with the addition of training on how to replace the cartridge.
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`30. Dr. Goland identifies several co-morbidities with diabetes that might
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`affect a patient’s ability to use a pen. EX2111, ¶¶22-25. While I disagree with her
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`assessment on how “common” many of these co-morbidities are, they were all well-
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`known at the filing date and were factored into patients’ care plans. Indeed, existing
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`pens were considered to have met the needs of patients with “special challenges” yet
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`capable of using a pen. EX1046, 68. Significantly, Dr. Goland does not identify any
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`case in which a change in pen made a difference for a patient with one of these co-
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`morbidities. Again, in my experience, a patient who was incapable of using a pen
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`would not have been aided by a switch to a different pen because the differences
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`between pens (including differences in injection force) are too slight to make a
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`practical difference; instead such patients would be switched to a different delivery
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`mode, possibly including caregiver assistance.
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`31. At the time of the 2003 filing (and even now), insulin syringes required
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`less injection force and permitted faster injection than insulin pens. At that time, when
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`most patients used syringes anyway, if injection force had been an issue, the patient
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`would have been best served using a pre-loaded syringe.
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`32.
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`In sum, at the 2003 filing date, there was no unmet need for a disposable
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`pen to deliver insulin with less injection force, much less the pen described in the
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`contested claims. The real need—reliable delivery of insulin—was already being
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`adequately met through syringes and existing pens. Individual patient difficulties were
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`(and continue to be) addressed through training in the use of the device and other
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`forms of support, such as pre-loading syringes. EX1045, 523 (stressing importance of
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`training).
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`B. No long-felt, unmet need for the claimed pen
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`33.
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`I note that Dr. Goland’s declaration does not discuss the claims at all
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`except to note that they are being reviewed for unpatentability. EX2111, 1.
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`34.
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`I also note that the contested claims do not facially reflect Dr. Goland’s
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`concern for treating elderly diabetic patients or diabetic patients with dexterity or
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`other mobility problems. Indeed, the claims do not mention insulin, diabetes, or lower
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`injection force or thumb extension. The claims do not distinguish between types of
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`insulin, for example, fast-acting or long-acting.
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`35. While Dr. Goland emphasizes an “easy to use” pen as “important” for
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`patient adherence (EX2111, ¶14), in my experience many other factors are more
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`important. Of these, cost is easily the greatest obstacle to adherence. Indeed, in recent
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`years when insulin prices have been soaring, I spend one-third of the appointment on
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`average addressing the patient’s issues with affordability. There is no question that the
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`greatest “ease of use” factor is affordability: an unaffordable pen is no use at all.
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`1. Background and Treatments
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`36. Diabetes mellitus is a metabolic disorder affecting an increasing number
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`of Americans. According to the Center for Disease Control and Prevention (“CDC”)
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`over 30 million Americans (nearly 10% of the population) suffer from diabetes. While
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`there are many types of diabetes, Type 2 (insulin insensitivity) accounts for 90-95% of
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`the cases. Diabetes is the seventh leading cause of death in this country. Average
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`medical expenditures for patients diagnosed with diabetes is about 2.3 times the
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`average medical expenditures for non-diabetic patients. EX1044.
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`37. Dr. Goland notes that insulins come in at least three forms, rapid-,
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`intermediate-, and long-acting. EX2111, ¶18. Within these forms, there can be
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`differences that also affect insulin choice. For example, Lantus and Levemir are two
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`long-acting insulins. Lantus tends to last a bit longer than Levemir, which is helpful
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`for patients prone to waking up in the morning with hyperglycemia (known as the
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`“dawn effect”); but Lantus is relatively acidic and may sting when injected, which
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`some patients cannot tolerate. Skilled clinicians consider product differences like
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`these in determining which insulin is most suitable for an individual patient.
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`38. Dr. Goland provides percentages for her patients using insulin but does
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`not explain the reasons for those percentages or why they sum to less than 100%. In
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`my practice, at any given point in time, about 60% of my diabetic patients are not
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`using insulin. Many patients who do use insulin use pumps. These patients (not using
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`insulin or using pumps) probably account for most of Dr. Goland’s missing patients.
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`Differences in cost likely account for at least some of the patients using intermediate-
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`rather than long-acting insulin. Given the high cost of long-acting insulins, I am
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`increasingly seeing patients switching back to older, intermediate-acting insulins for
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`cost reasons.
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`2. Lantus and SoloStar
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`39. While several different insulin products use the SoloStar pen, not all of
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`them are long-acting insulin. For example, Apidra and Admelog are fast-acting insulin
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`products available in a SoloStar pen. EX2109, ¶22. Dr. Goland’s testimony only
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`purports to identify a long-felt unmet need for a disposable pen filled with long-acting
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`insulins. In my experience, at the filing date, there was no long-felt unmet need for yet
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`another insulin pen for fast- or for long-acting insulins.
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`40. Prior to the 2003 filing date, several long-acting insulins were available,
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`including Lantus. Two products, protamine zinc insulin (or PZI) and ultralente, had
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`been used for decades prior to the introduction of Lantus.
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`41. Lantus is currently available in vials and in Sanofi’s proprietary
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`disposable pen, SoloStar. Sanofi does not make a reusable pen for the American
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`market, although Sanofi does market insulin pen cartridges for use in reusable pens in
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`other countries.
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`42. Before SoloStar, Sanofi had supplied Lantus in a reusable pen, OptiClik,
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`that used Lantus cartridges. However, many of my patients reported that Sanofi’s
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`OptiClik pen was difficult to refill and unreliable about delivering accurate doses. See
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`EX1045, 528, Table 2 (showing marked deviation in dosing for OptiClik pens, and
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`mediocre performance for SoloStar pens). Patients complained that the OptiClik pen
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`was not working. In my practice, OptiClik was the only truly bad pen that we
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`experienced.
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`43. On its introduction, SoloStar was welcomed by Lantus users as a
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`significant improvement over Sanofi’s defective OptiClik pen but was not recognized
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`as an unusually good pen in itself.
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`44.
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`I did not switch any patients from other pens (other than OptiClik) to
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`SoloStar, except as an indirect consequence of switching a patient to Lantus as the
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`preferred insulin. I am unaware of any other clinician switching a patient to SoloStar
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`simply because of the properties of the pen. I note that Dr. Goland, despite having
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`practiced at the relevant time, does not indicate that she switched any of her patients to
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`SoloStar solely or even partially because of its purported ease of use. Again, insulin
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`drives the prescription, with the delivery mode being determined by the modes
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`available from the prescribed insulin’s manufacturer. SoloStar is prescribed frequently
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`(in my practice and elsewhere) because Lantus is a popular insulin, not because it is a
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`remarkable pen.
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`3. Comparison to OptiClik, FlexPen, and other available pens
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`45. Dr. Goland notes that at least two pens with long-acting insulin pre-date
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`SoloStar—Sanofi’s own OptiClik and Novo Nordisk’s FlexPen—but omits other pens
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`from her analysis solely because they use a different type of insulin. EX2111, ¶¶27-
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`30. She entirely overlooks other alternative pens—like the Disetronic pen, which
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`could be used with any kind of insulin. (H. See EX1046, 61, 62-63 (discussing the
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`Disetronic pen, listing some of the available insulin pens).
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`46. While Dr. Goland restricts her focus to “easy to use, disposable” pens
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`(EX2111, ¶27) , the available pens were already considered easy to use both generally
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`and for patients with “special challenges”. Id., 57, 68. The emphasis on “disposable”
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`is meaningless in this context because pens are largely fungible and patients have, if
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`anything, a preference for reusable pens when they are available for the same
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`prescribed insulin. EX1047.
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`47. The FlexPen is a disposable pen that was already considered easy to use
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`despite the slight differences in injection force that Dr. Goland perceives as
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`significant. EX1046, 57.2 The Bohannon article is consistent with my experience,
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`2 I note that while the author of the Bohannon article (EX1046, 68) reports a
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`connection with Novo Nordisk (maker of the FlexPen), many of the authorities on
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`which Dr. Goland relies have connections to Sanofi. For example, EX2116, 9 (Sanofi
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`assisted, edited); EX2123, 1 (Sanofi affiliate); EX2126, 4 (Sanofi supported); EX2140
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`(Sanofi sponsored, edited) EX2143, 10 (Sanofi sponsored); EX2144, 2 (Sanofi
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`author); EX2184, 3 (purchased content); EX2185 (Sanofi press release).
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`while the inferences that Dr. Goland draws are not. Dr. Goland does not indicate that
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`she ever switched a patient from FlexPen to SoloStar solely on the basis of injection
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`force.
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`48. Dr. Goland also identifies “suboptimal” dose-stop features in the
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`FlexPen. EX2111, ¶29. In my experience, this was not a problem for patients. Because
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`each delivery form has its own protocols, clinicians know that patients must be trained
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`on the use of the specific equipment involved. With proper training, patients
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`experienced (and continue to experience) great success with the FlexPen, which is still
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`on the market. See, for example, EX1057, 5 (showing FlexPen currently used with
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`Novolog, a rapid-acting insulin). Dr. Goland also fails to note relative FlexPen
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`advantages, such as its markedly shorter injection time compared to SoloStar.
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`EX1045, 526 (reporting 10 seconds for SoloStar, 6 seconds for FlexPen).
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`49. Dr. Goland is correct that Sanofi’s OptiClik pen was unsatisfactory, but I
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`disagree with the reasons she gives. First, OptiClik was a reusable pen, not a
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`disposable pen, so to the extent Sanofi considers the distinction between disposable
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`and reusable pens to be significant, this comparison is wrong. While OptiClik was
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`difficult to use, in my experience, patient complaints focused on the difficulty in
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`reloading cartridges into the pen and the difficulty in getting reliable doses. EX1045,
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`528 (noting OptiClik less trusted than FlexPen). In my experience, the latter problem
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`was the major concern for patients using OptiClik because diabetes patients must
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`Dr. William Biggs Declaration
`
`-17-
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`Mylan Ex.1048
`Mylan v. Sanofi - IPR2018-01676
`
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`
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`closely regulate their insulin use, which makes unreliable dosing counterproductive.
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`Patients just did not trust OptiClik. My patients did not express concerns about
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`injection force.
`
`50. Dr. Goland states that OptiClik’s bulkiness was also a disadvantage.
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`EX2111, 28. While Opticlik was a bit wider than SoloStar, width is not necessarily a
`
`disadvantage because it can aid patients with grip or agility problems. For example,
`
`the Basaglar pen (below, bottom pen) is relatively bulky to enhance gripping. The
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`major problem with Opticlik was unreliability, not width. In any case, I note that the
`
`contested claims do not address bulkiness.
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`
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`Dr. William Biggs Declaration
`
`-18-
`
`Mylan Ex.1048
`Mylan v. Sanofi - IPR2018-01676
`
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`
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`51. Dr. Goland discusses but dismisses other then-available pens because
`
`they did not use long-acting insulins. Again, the relevance of her testimony to the
`
`present claims is not explained. As far as I can tell, the claims are not limited to long-
`
`acting insulin. Indeed, as discussed above (¶39), SoloStar itself is used with both fast-
`
`and long-acting insulins.
`
`52. Dr. Goland also concludes without explanation that these other pens
`
`(Humalog/Humulin, NovoPen3 and AutoPen Classic) “suffered from some of the
`
`same drawbacks”. EX2111, ¶30. It is not clear which drawbacks she means, which is
`
`important because most of the drawbacks she discusses are not relevant to the
`
`question of unmet need. In any case, her assertion is not consistent with my
`
`experience with these pens, which was that these very pens were regarded as easy to
`
`use. EX1046, 57, 62-63.
`
`4. Background and Treatments
`
`53.
`
` Dr. Goland states that “[t]he Lantus® SoloSTAR® pen fulfilled the
`
`long-felt, but unmet need for an easy-to-use, low injection force pen for administering
`
`a long-acting insulin glargine formulation.” This conclusion is deeply misleading. At
`
`the filing date, insulin glargine was only available as Sanofi’s Lantus. Thus, if insulin
`
`glargine was not available in an adequate pen, this unavailability was the result of
`
`marketing decisions by Sanofi; for example, only supplying Lantus in the defective
`
`Dr. William Biggs Declaration
`
`-19-
`
`Mylan Ex.1048
`Mylan v. Sanofi - IPR2018-01676
`
`
`
`
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`OptiClik pen and not making it available in cartridges for other pens, such as the
`
`AutoPen. Sanofi’s marketing decisions are not a technological problem.
`
`54.
`
`In paragraphs 31-41, Dr. Goland lists purported advantages of the
`
`SoloStar pen. While I do not agree with all of her conclusions, I do agree that SoloStar
`
`is an adequate pen for delivering Lantus, a specific insulin that I often prescribe. Said
`
`another way, I like prescribing Lantus SoloStar because I like prescribing Lantus, not
`
`because the SoloStar pen offers any unique advantage to my patients.
`
`55. Apart from the dubious benefit of lower injection force, Dr. Goland
`
`reports several other advantages involving dialing, portability, feedback and ease of
`
`handling. Significantly, she does not report that these advantages were unique to
`
`SoloStar. They were not. For example, while some pens would require greater dial
`
`extension, requiring greater thumb extension, my recollection is that the Disetronic
`
`pen did not. The difference between the maximum extension for SoloStar and the
`
`FlexPen is difficult to discern visually, as my photograph (below) showing SoloStar
`
`(top) and FlexPen (bottom) indicates. The difference is too slight to be of practical
`
`consequence. Similarly, while inaccurate dosing is a serious problem, not all pens
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`suffered this problem. The significant outlier was Sanofi’s own OptiClik pen, but it
`
`was not typical of insulin pens in its unreliability.
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`Dr. William Biggs Declaration
`
`-20-
`
`Mylan Ex.1048
`Mylan v. Sanofi - IPR2018-01676
`
`
`
`
`
`
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`56. Dr. Goland also lauds SoloStar as “the first 80U pen” (EX2111, ¶38), but
`
`she is wrong. Once again, at least the Disetronic pen offered this feature years earlier.
`
`EX1046, 82-83 (Table 2: “Minimum/maximum dose (units) … 1/80”). Opticlik also
`
`provided 80U dosing. There is nothing magic about an 80U dose: pens typically have
`
`300U of insulin. Many patients require less than 60U per injection, while as Dr.
`
`Goland notes (EX1056, 60:14-17) some patients require more than 100U per dose.
`
`There were easy work-arounds such as redialing the dose during the injection to
`
`provide the additional amount. None of my patients has ever been held back from
`
`Dr. William Biggs Declaration
`
`-21-
`
`Mylan Ex.1048
`Mylan v. Sanofi - IPR2018-01676
`
`
`
`
`
`getting the insulin they need by the maximum dial setting on a pen, whether it is 60U
`
`or 80U. For large doses of insulin glargine, a recent study confirmed that the long-
`
`standing practice of going to twice-daily dosing is the better choice anyway. EX1059,
`
`35 (“The first report on using insulin glargine twice daily was published shortly after
`
`its availability”) and 36 (“In conclusion, twice daily insulin glargine results in a
`
`significant improvement in glucose control in selected patients with type 2 diabetes.”).
`
`There was no unmet need in 2003 for an 80U pen and there is no specific need for an
`
`80U pen today.
`
`57. Dr. Goland lauds the disposability of SoloStar, but again other disposable
`
`pens existed years earlier. EX1046, 58 (discussing the pros and cons of “prefilled”
`
`versus reusable pens). As noted above, in my experience, patients generally prefer
`
`reusable pens when they are available for their greater reliability and long-term cost-
`
`savings. In any case, Dr. Goland never explains what need disposability was supposed
`
`to have solved that had not already been solved.
`
`58. Finally, Dr. Goland cites various studies touting how easy SoloStar is to
`
`use and speculating on what advantages it might offer. Fortunately, clinicians are a
`
`sophisticated audience and know to look at the study sponsors when evaluating such
`
`reports. The studies she cites in support of SoloStar are generally sponsored by
`
`Dr. William Biggs Declaration
`
`-22-
`
`Mylan Ex.1048
`Mylan v. Sanofi - IPR2018-01676
`
`
`
`
`
`Sanofi.3 This does not mean that SoloStar is not a good pen, but it would lead a
`
`clinician to question whether any of the marginal benefits the studies identify would
`
`have any actual clinical relevance. For the reason discussed above, in my experience,
`
`patients and clinicians saw SoloStar as simply Sanofi’s proprietary pen for delivering
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`Lantus with no clinically relevant differences from other pens apart from its use of a
`
`particularly desired insulin.
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`III.
`
`CONCLUSION
`59. The most striking thing about Dr. Goland’s declaration is what she did
`
`not say: that she ever switched a patient to Lantus SoloStar for any of the reasons she
`
`
`3 Some of the methodologies were odd. For example, in EX2123, a Sanofi
`
`sponsored study in which the investigators did not generate the data for SoloStar (see
`
`notes to tables 1-3), the needles were different for the different tests (EX2123, 2),
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`which does not reflect actual patient use and suggests the possibility that the testing
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`was manipulated to suit Sanofi’s pens. Needle characteristics will affect the required
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`injection force, thus potentially distorting the results. EX1053, 68:3-87:5. Moreover,
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`injection force was measured by injecting over paraffin, without touching the paraffin.
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`EX2123, 3. Again, this is nothing like real-world patient use. This would lead a
`
`reasonable clinician t
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