UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
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`
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`COALITION FOR AFFORDABLE DRUGS VIII, LLC
`Petitioner,
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`v.
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`THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
`Patent Owner
`
`______________
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`Case: IPR2015-01836
`Patent No. 7,932,268
`______________
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`DECLARATION OF THOMAS A. BAILLIE, PH.D., D.SC.
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`TABLE OF CONTENTS
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`I. Summary of Opinions .......................................................................................... 1
`II. Materials Considered ........................................................................................ 3
`III. Qualifications .................................................................................................... 3
`IV. The Patents-At-Issue ........................................................................................ 6
`A. The ’268 Patent ............................................................................................. 6
`1. Overview ....................................................................................................... 6
`2. Existing Claims ............................................................................................. 7
`3. Proposed Claim Amendment ........................................................................ 8
`B. The ’135 Patent ........................................................................................... 10
`1. Overview ..................................................................................................... 10
`2. Existing Claims ........................................................................................... 11
`3. Proposed Claim Amendment ...................................................................... 15
`V. Legal Principles .............................................................................................. 18
`A.
`Patent Validity ............................................................................................. 19
`B. The Person of Ordinary Skill in the Art ...................................................... 19
`C. Obviousness ................................................................................................. 21
`VI. Opinions .......................................................................................................... 22
`A. Tutorial ........................................................................................................ 22
`1. Understanding the relationship between a drug’s PK and PD properties is
`required to design an optimal dosing regimen. ................................................. 23
`2. The chemical structure of a drug determines its PK and PD properties. .... 28
`3. MTP inhibitors have a distinct mechanism of action and toxicity profile. . 36
`B. Obviousness ................................................................................................. 39
`1. Dr. Mayersohn does not address the differences between lomitapide and
`implitapide. ........................................................................................................ 40
`2. Dr. Mayersohn overstates the teachings of Stein and Pink Sheet 2004. ..... 51
`3. Dr. Mayersohn’s obviousness combinations fail to establish either a
`motivation to combine or a reasonable expectation of success. ........................ 54
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`4. Secondary considerations favor non-obviousness. ..................................... 64
`5. Conclusion ................................................................................................... 70
`6. Proposed Claim Amendment ...................................................................... 71
`VII. Conclusion ................................................................................................... 72
`VIII. Prior Expert Testimony ............................................................................... 72
`IX. Compensation ................................................................................................. 73
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`1.
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`I, Thomas A. Baillie, have been retained to testify on behalf of Patent
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`Owner the Trustees of the University of Pennsylvania (“Penn”) in this proceeding
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`as an expert in medicinal chemistry and pharmacology.
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`I.
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`SUMMARY OF OPINIONS
`2.
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`I am aware that Petitioner Coalition for Affordable Drugs VIII, LLC
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`(“CFAD”) has sought to challenge the validity of U.S. Patents Nos. 7,932,268
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`(“the ’268 patent”) and 8,618,135 (“the ’135 patent”) (collectively, the “patents-at-
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`issue”) in separate Inter Partes Review (“IPR”) proceedings before the Patent Trial
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`and Appeal Board (“PTAB”) of the United States Patent and Trademark Office. I
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`am also aware that PTAB has instituted IPR proceedings with respect to each of
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`the patents-at-issue.
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`3.
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`I am aware that Penn is the sole assignee and owner of the patents-at-
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`issue, and that rights to the patent have been licensed to Aegerion Pharmaceuticals,
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`Inc. (“Aegerion”). I am also aware that Aegerion currently markets the drug
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`compound lomitapide in the United States under the trade name JUXTAPID®.
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`4.
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`I have been retained to address the assertions in the Declaration of
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`Michael Mayersohn, Ph.D. (CFAD Ex. 1003, “Mayersohn Dec.”) and the
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`Declaration of Randall J. Zusman, M.D. (CFAD Ex. 1002, “Zusman Dec.”)
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`regarding the alleged invalidity of the patents-at-issue. In my Declaration, I
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`IPR2015-01836
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`provide my opinions regarding the relationship between a drug compound’s
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`chemical structure and its pharmacological effects, and how that relationship has
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`an impact on the dosing of the drug to patients. It is my opinion that the claims of
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`the patents-at-issue are not invalid for obviousness for at least the following
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`principal reasons: (1) implitapide and lomitapide have important differences in
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`chemical structure that would preclude an expectation that they could be dosed in
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`the same manner; (2) a person of ordinary skill in the art would not have had a
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`reasonable expectation of success in applying the implitapide protocol mentioned
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`in either “Bayer/PPD Implitapide Development Follows Zetia Model”, THE PINK
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`SHEET, Vol. 66, No. 7, p. 17 (2004) (CFAD Ex. 1013, “Pink Sheet 2004”) or Evan
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`Stein, “Microsomal Triglyceride Transfer Protein (MTP) Inhibitor (implitapide)
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`program”, Presentation Given at PPD’s Analyst Day (February 5, 2004) (CFAD
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`Ex. 1014, “Stein”) to lomitapide; (3) the obviousness combinations offered by
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`CFAD, Dr. Zusman and Dr. Mayersohn establish neither a motivation to combine
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`nor a reasonable expectation of success; and (4) secondary considerations, namely
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`failure of others and unexpected results, further demonstrate non-obviousness.
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`5.
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`Additionally, I have been asked to address the non-obviousness of
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`certain proposed claims that I understand Penn has submitted with its Motion to
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`Amend in these proceedings. As explained in further detail below, and for reasons
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`similar to those set forth above, it is my opinion that the proposed claims are
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`patentable and not obvious based on the prior art.
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`II. MATERIALS CONSIDERED
`6.
`In forming my opinions and views expressed in this declaration, I
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`have relied upon my knowledge, education and training, as well as my many years
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`of experience in the field of medicinal chemistry, as reflected in my qualifications
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`and credentials set forth below and in my curriculum vitae, Penn Ex. 2028. I have
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`also considered the documents cited herein and the documents listed in Penn Ex.
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`2032.
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`III. QUALIFICATIONS
`7.
`I am Professor of Medicinal Chemistry and Dean Emeritus of the
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`School of Pharmacy at the University of Washington in Seattle, WA, USA. I
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`served as Dean of that School between 2008-2014 and, in addition, I held the
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`position of Vice Provost for Strategic Initiatives at the same institution between
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`2012-2014. Immediately prior to assuming the above responsibilities at the
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`University of Washington, I spent 14 years in the pharmaceutical industry at Merck
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`Research Laboratories (1994-2008), culminating as Global Vice President of Drug
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`Metabolism & Pharmacokinetics in West Point, PA, USA.
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`8. My academic training was in chemistry and biochemistry. I received
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`my Bachelor of Science with First Class Honors in chemistry (1970), a Ph.D. in
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`organic chemistry (1973), and a Doctor of Science in chemistry (1992), all from
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`Glasgow University in Scotland. I also was awarded an M.Sc. degree in
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`biochemistry from the University of London (1978). In 2010, I was elected a
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`Fellow of the Royal Society of Chemistry and, the following year, I was elected an
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`American Chemical Society Fellow.
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`9.
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`Following postdoctoral training in steroid biochemistry at the
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`Karolinska Institute in Stockholm, Sweden (1973-1975), I held successive faculty
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`appointments at the Royal Postgraduate Medical School, University of London
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`(1975-1978), the School of Pharmacy at the University of California San Francisco
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`(1978-1981), and the School of Pharmacy at the University of Washington (1981-
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`1994) where I was promoted to Full Professor in 1988. I retired from the
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`University of Washington in 2016.
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`10. While at Merck Research Laboratories (1994-2008), I had global
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`oversight responsibility for Merck’s drug metabolism and pharmacokinetics
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`(DMPK) function, and served as the DMPK representative on the Preclinical
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`Development Review Committee (the executive group charged with
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`recommending new chemical entities for advancement into development), chairing
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`that group from 2007-2008. This position also gave me the opportunity to work on
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`numerous drug programs relating to hypercholesterolemia.
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`11. Over the course of my career, the focus of my research has been in the
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`field of foreign compound metabolism in animals and humans, with an emphasis
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`on the application of mass spectrometric techniques to explore the relationship
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`between drug metabolism and the generation of products with pharmacological or
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`toxicological activity. I have led numerous research studies in these areas, both in
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`academia and in the pharmaceutical industry. I have authored or co-authored some
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`240 peer-reviewed publications, review articles, book chapters, and conference
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`proceedings.
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`12.
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`I served as Editor of the journal Chemico-Biological Interactions
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`(1990-1997), and am, or have been, a member of the editorial advisory boards of
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`the following journals: Drug Metabolism and Disposition, Drug Metabolism
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`Reviews, Chemical Research in Toxicology, Modern Mass Spectrometry, Rapid
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`Communications in Mass Spectrometry, Journal of Labelled Compounds and
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`Radiopharmaceuticals, Biological Mass Spectrometry, Life Sciences, Mass
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`Spectrometry Reviews, Journal of Mass Spectrometry, and Drug Discovery Today:
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`Technologies.
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`IPR2015-01836
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`13. Prior to and following my career in industry, I have served as a
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`consultant to the pharmaceutical industry on issues related to drug metabolism and
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`preclinical drug development, and I have contributed to the construction of
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`regulatory science policy through participation in joint activities between the US
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`Pharmaceutical Research & Manufacturers Association (PhRMA) and the US Food
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`& Drug Administration (FDA).
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`IV. THE PATENTS-AT-ISSUE
`A. The ’268 Patent
`1. Overview
`14. The ’268 patent, entitled “Methods for treating disorders or diseases
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`associated with hyperlipidemia and hypercholesterolemia while minimizing side
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`effects”, was issued to Daniel J. Rader on April 26, 2011. The ’268 patent was
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`filed on March 7, 2005, and claims priority to Provisional U.S. Patent Application
`
`No. 60/550,915 (“the ’915 Provisional”), which was filed on March 5, 2004.
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`15. The claims of the ’268 patent are generally directed to methods of
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`treating hyperlipidemia or hypercholesterolemia in humans via the administration
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`of the MTP inhibitor lomitapide. Recitations of the individual claims of are
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`2.
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`1
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`6. Claimm 1 is direccted to “A
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`om uffering froa subject sumethod off treating a
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`Existing Claims
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`hyperlippidemia orr hyperchollesterolemia, the metthod comp
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`rising admministering
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`to
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`the subjject an effeective amount of an MMTP inhib
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`itor, whereein said addministratioon
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`three step
`comprisses at least
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`-wise, incrreasing dosse levels o
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`f the MTP
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` inhibitors
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`whereinn a first dosse level is from abouut 2 to abouut 13 mg/dday, a seconnd dose levvel
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`is from about 5 to
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`about 30 mmg/day, annd a third ddose level iis from aboout 10 to
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`about 500 mg/day; and whereein the MTTP inhibitorr is represeented by:
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`or a phaarmaceuticcally accepttable salt thereof or tthe piperiddine N-oxidde thereof,
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`and
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`whereinn each dosee level is administereed to the suubject for aabout 1 to 44 weeks.”
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`17. Claimm 2 is direccted to “Thhe method
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`severe hhypercholeesterolemiaa.”
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`18. Claimm 3 is direccted to “Thhe method
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`of claim 11 wherein tthe disordeer is
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`of claim 1
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`1 wherein oone or morre of
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`Total C
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`holesterol,, LDL, fastting triglyccerides (TGG), VLDL,, lipoproteiin (a) (Lp(
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`a)),
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`and-lipooprotein B are reduceed by at leaast 15%, coompared too control leevels.”
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`PEENN EX. 22024
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`PPR2015-011836
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`19. Claim 4 is directed to “The method of claim 1 wherein one or more of
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`Total Cholesterol, LDL, fasting triglycerides (TG), VLDL, lipoprotein (a) (Lp(a)),
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`and-lipoprotein B are reduced by at least 25%, compared to control levels.”
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`20. Claim 5 is directed to “The method of claim 1 wherein the MTP
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`inhibitor is administered orally.”
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`21. Claim 6 is directed to “The method of claim 1 wherein said increasing
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`dose levels further comprise a fourth dose level.”
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`22. Claim 7 is directed to “The method of claim 1 wherein said increasing
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`dose levels further comprise a fourth and a fifth dose level.”
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`23. Claim 8 is directed to “The method of claim 1, wherein the increasing
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`dose levels comprise a fourth dose level from about 20 to about 60 mg/day and a
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`fifth dose level from about 30 to about 75 mg/day.”
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`Proposed Claim Amendment
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`3.
`I am aware that Penn has proposed an amendment to the claims of the
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`24.
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`’268 patent in the event the PTAB finds the original claims unpatentable. I
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`understand that in its Motion to Amend, Penn has proposed cancellation of all the
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`existing claims of the ’268 patent and adding six substitute claims, denoted claims
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`9-14.
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`PENN EX. 2024
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`IPR2015-01836
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`25. Substitute claim 9 reads as follows: “A method of treating a subject
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`suffering from hyperlipidemia or hypercholesterolemia, the method comprising
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`administering to the subject an effective amount of an MTP inhibitor, wherein said
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`administration comprises at least three stepwise, increasing dose levels of the MTP
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`inhibitors, wherein a first and a second dose level is 50% of the immediately
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`following dose level, and wherein a third dose level is from about 0.2 to about 0.59
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`mg/kg/day based on a weight between 62.5 and 74.9 kg, and wherein the MTP
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`inhibitor is N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4’-(trifluoromethyl)[1,1’-biphenyl]-
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`2-yl] carbonyl] amino]-1-piperidinyl]butyl]-9H-fluorene-9-carboxamide,
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`methanesulfonate, and wherein each dose level is administered to the subject for
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`about 1 to 4 weeks”.
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`26. Substitute claim 10 reads as follows: “The method of claim 9 wherein
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`the disorder is severe hypercholesterolemia”.
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`27. Substitute claim 11 reads as follows: “The method of claim 9 wherein
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`one or more of Total Cholesterol, LDL, fasting triglycerides (TG), VLDL,
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`lipoprotein (a) (Lp(a)), and-lipoprotein B are reduced by at least 15%, compared to
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`control levels”.
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`28. Substitute claim 12 reads as follows: “The method of claim 9 wherein
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`one or more of Total Cholesterol, LDL, fasting triglycerides (TG), VLDL,
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`9
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`IPR2015-01836
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`lipoprotein (a) (Lp(a)), and-lipoprotein B are reduced by at least 25%, compared to
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`control levels”.
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`29. Substitute claim 13 reads as follows: “The method of claim 9 wherein
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`the MTP inhibitor is administered orally”.
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`30. Substitute claim 14 reads as follows: “The method of claim 9 wherein
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`said increasing dose levels further comprise a fourth dose level”.
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`31.
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`I am not offering any opinion as to either (1) the effective date of
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`invention for these substitute claims or (2) whether these substitute claims properly
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`claim priority to the ’915 provisional.
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`32. That said, the opinions I have offered below with respect to
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`obviousness apply equally well both to the original claims of the ’268 patent and to
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`the amended claims proposed by Penn. This means that my opinions that the
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`claimed subject matter would not have been obvious to a POSA apply whether or
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`not the PTAB grants Penn’s proposed amendment.
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`B.
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`The ’135 Patent
`1. Overview
`33. The ’135 patent, entitled “Methods for treating disorders or diseases
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`associated with hyperlipidemia and hypercholesterolemia while minimizing side
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`effects”, was issued to Daniel J. Rader on December 31, 2013. The ’135 patent
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`was filed on March 11, 2011, and claims priority to Provisional U.S. Patent
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`Application No. 60/550,915 (“the ’915 Provisional”), which was filed on March 5,
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`2004, and to the ’268 patent, which was filed on March 7, 2005. The ’135 patent is
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`a continuation of the ’268 patent, which I understand means they share the same
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`specification.
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`34. The claims of the ’135 patent are generally directed to methods of
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`treating hyperlipidemia or hypercholesterolemia in humans via the administration
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`of the MTP inhibitor lomitapide. Recitations of the individual claims of are
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`provided below.
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`2.
`Existing Claims
`35. Claim 1 is directed to “A method of treating a subject suffering from
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`hyperlipidemia or hypercholesterolemia, the method comprising administering to
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`the subject an effective amount of an MTP inhibitor, wherein said administration
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`comprises at least three step-wise, increasing dose levels of the MTP inhibitor
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`wherein a first dose level is from about 2 to about 13 mg/day, a second dose level
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`is from about 5 to about 30 mg/day, and a third dose level is from about 10 to
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`about 50 mg/day; and wherein the MTP inhibitor is represented by:
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`11
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`or a phaarmaceuticcally accepttable salt t
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`de thereof, dine N-oxidhereof or tthe piperid
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`and
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`whereinn each dosee level is administereed to the suubject for aabout 1 to aabout 5
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`weeks.””
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`36. Claimm 2 is direccted to “Thhe method
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`severe hhypercholeesterolemiaa.”
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`37. Claimm 3 is direccted to “Thhe method
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`of claim 11 wherein tthe disordeer is
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`of claim 1
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`1 wherein oone or morre of
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`Total C
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`holesterol,, LDL, fastting triglyccerides (TGG), VLDL,, lipoproteiin (a) (Lp(
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`a)),
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`and apoolipoproteinns A-I, A-III, B, and EE are reducced by at leeast 15%,
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`compared
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`to
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`control levels.”
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`3
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`8. Claimm 4 is direccted to “Thhe method
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`of claim 11 wherein oone or morre of
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`Total C
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`holesterol,, LDL, fastting triglyccerides (TGG), VLDL,, lipoproteiin (a) (Lp(
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`a)),
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`compared
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`to
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`and apoolipoproteinns A-I, A-III, B, and EE are reducced by at leeast 25%,
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`control levels.”
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`3
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`9. Claimm 5 is direccted to “Thhe method
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`of claim 11 wherein tthe MTP
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`inhibitoor is administered oraally.”
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`40. Claim 6 is directed to “The method of claim 1 wherein said increasing
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`dose levels further comprise a fourth dose level.”
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`41. Claim 7 is directed to “The method of claim 1 wherein said increasing
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`dose levels further comprise a fourth and a fifth dose level.”
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`42. Claim 8 is directed to “The method of claim 7 wherein said fourth
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`dose level is from about 20 to about 60 mg/day, and said fifth dose level is from
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`about 30 to about 75 mg/day.”
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`43. Claim 9 is directed to “A method of treating a subject suffering from
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`hyperlipidemia or hypercholesterolemia, the method comprising administering to
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`the subject an effective amount of an MTP inhibitor, wherein said administration
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`comprises at least three step-wise, increasing dose levels of the MTP inhibitor
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`wherein a first dose level is from about 2 to about 13 mg/day, administered to the
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`subject for about 2 weeks; a second dose level is from about 5 to about 30 mg/day,
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`administered to the subject for about 2 weeks to about 4 weeks; and a third dose
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`level is from about 10 to about 50 mg/day, administered to the subject for about 2
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`weeks to about 4 weeks; and wherein the MTP inhibitor is represented by:
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`13
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`or a phaarmaceuticcally accepttable salt thereof or tthe piperiddine N-oxidde thereof.
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`444. Claimm 10 is direected to “AA method oof treating
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`hyperlippidemia orr hyperchollesterolemia, the metthod comp
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`the subjject an effeective amount of an MMTP inhib
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`itor, whereein said addministratioon
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`three step
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`-wise, incrreasing dosse levels o
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`a subject ssuffering frfrom
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`rising admministering
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`to
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`whereinn a first dosse level is from abouut 2 to abouut 13 mg/dday, adminiistered to tthe
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`subject for about 11 to about 12 weeks; a second ddose level
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`is from abbout 5 to abbout
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`and a thirdd dose leveel is
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`30 mg/dday, adminnistered to tthe subjectt for aboutt 4 weeks;
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`from abbout 10 to aabout 50 mmg/day, admministered
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`to the subjbject for ab
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`out 4 weekks;
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`and wheerein the MMTP inhibiitor is repreesented byy:
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`or a phaarmaceuticcally accepttable salt thereof or tthe piperiddine N-oxidde thereof.
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`PEENN EX. 22024
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`CFAD v. PEENN
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`PPR2015-011836
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`CI
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`14
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`Proposed Claim Amendment
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`3.
`I am aware that Penn has proposed an amendment to the claims of the
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`45.
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`’135 patent in the event the PTAB finds the original claims unpatentable. I
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`understand that in its Motion to Amend, Penn has proposed cancellation of all the
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`existing claims of the ’135 patent and adding eight substitute claims, denoted
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`claims 11-18.
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`46. Substitute claim 11 reads as follows: “A method of treating a subject
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`suffering from hyperlipidemia or hypercholesterolemia, the method comprising
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`administering to the subject an effective amount of an MTP inhibitor, wherein said
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`administration comprises at least three stepwise, increasing dose levels of the MTP
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`inhibitors, wherein a first and a second dose level is 50% of the immediately
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`following dose level, and wherein a third dose level is from about 0.2 to about 0.59
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`mg/kg/day based on a weight between 62.5 and 74.9 kg; and wherein the MTP
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`inhibitor is N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4’-(trifluoromethyl)[1,1’-biphenyl]-
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`2-yl] carbonyl] amino]-1-piperidinyl]butyl]-9H-fluorene-9-carboxamide,
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`methanesulfonate, and wherein each dose level is administered to the subject for
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`about 1 to 5 weeks”.
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`47. Substitute claim 12 reads as follows: “The method of claim 11
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`wherein the disorder is severe hypercholesterolemia”.
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`15
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`

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`48. Substitute claim 13 reads as follows: “The method of claim 11
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`wherein one or more of Total Cholesterol, LDL, fasting triglycerides (TG), VLDL,
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`lipoprotein (a) (Lp(a)), and apolipoproteins A-I, A-II, B, and E are reduced by at
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`least 15%, compared to control levels”.
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`49. Substitute claim 14 reads as follows: “The method of claim 11
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`wherein one or more of Total Cholesterol, LDL, fasting triglycerides (TG), VLDL,
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`lipoprotein (a) (Lp(a)), and apolipoproteins A-I, A-II, B, and E are reduced by at
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`least 25%, compared to control levels”.
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`50. Substitute claim 15 reads as follows: “The method of claim 11
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`wherein the MTP inhibitor is administered orally”.
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`51. Substitute claim 16 reads as follows: “The method of claim 11
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`wherein said increasing dose levels further comprise a fourth dose level”.
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`52. Substitute claim 17 reads as follows: “A method of treating a subject
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`suffering from hyperlipidemia or hypercholesterolemia, the method comprising
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`administering to the subject an effective amount of an MTP inhibitor, wherein said
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`administration comprises at least three step-wise, increasing dose levels of the
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`MTP inhibitor, wherein a first dose level and a second dose level is 50% of the
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`immediately following dose level, wherein the first dose level is administered to
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`the subject for about 2 weeks; the second dose level is administered to the subject
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`16
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`

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`for about 2 weeks to about 4 weeks; and a third dose level is from about 0.2 to
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`about 0.59 mg/kg/day based on a weight between 62.5 and 74.9 kg, administered to
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`the subject for about 2 weeks to about 4 weeks; and wherein the MTP inhibitor is
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`N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4’-(trifluoromethyl)[1,1’-biphenyl]-2-yl]
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`carbonyl] amino]-1-piperidinyl]butyl]-9H-fluorene-9-carboxamide,
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`methanesulfonate”.
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`53. Substitute claim 18 reads as follows: “A method of treating a subject
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`suffering from hyperlipidemia or hypercholesterolemia, the method comprising
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`administering to the subject an effective amount of an MTP inhibitor, wherein said
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`administration comprises at least three step-wise, increasing dose levels of the
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`MTP inhibitor, wherein a first dose level and a second dose level is 50% of the
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`immediately following dose level, wherein the first dose level is administered to
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`the subject for about 1 to about 12 weeks; the second dose level is administered to
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`the subject for about 4 weeks; and a third dose level is from about 0.2 to about 0.59
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`mg/kg/day based on a weight between 62.5 and 74.9 kg, administered to the
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`subject for about 4 weeks; and wherein the MTP inhibitor is N-(2,2,2-
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`trifluoroethyl)-9-[4-[4-[[[4’-(trifluoromethyl)[1,1’-biphenyl]-2-yl] carbonyl]
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`amino]-1-piperidinyl]butyl]-9H-fluorene-9-carboxamide, methanesulfonate”.
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`17
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
`
`

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`54.
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`I am not offering any opinion as to either (1) the effective date of
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`invention for these substitute claims or (2) whether these substitute claims
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`properly claim priority to the ’915 provisional.
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`55. That said, the opinions I have offered below with respect to
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`obviousness apply equally well both to the original claims of the ’135 patent and to
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`the amended claims proposed by Penn. This means that my opinions that the
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`claimed subject matter would not have been obvious to a POSA apply whether or
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`not the PTAB grants Penn’s proposed amendment.
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`V. LEGAL PRINCIPLES
`56.
`I am not a lawyer and am not an expert in patent law. However,
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`counsel for Penn has provided me with a basic overview of the legal concepts
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`relevant to this case.
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`57.
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`I have reviewed the CFAD Petition Dated August 28, 2015 (Paper No.
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`1, “CFAD Pet.”) as well as the PTAB’s Institution Decision dated March 7, 2016
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`(Paper No. 7, “Institution Decision”), and I understand that the legal issue to be
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`decided in this case is whether the claims of the patents-at-issue are invalid as
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`obvious. CFAD Pet. at 4-5; Institution Decision at 6.
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`18
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`Patent Validity
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`I understand that it is a basic principle of patent law that the validity
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`A.
`58.
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`of each claim in a patent is determined individually. The determination of whether
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`a patent claim is valid requires that the language of the claim be compared to the
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`alleged prior art.
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`59.
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`I understand that in an IPR Proceeding each claim may be invalidated
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`only if the Petitioner proves by a preponderance of the evidence that the claims are
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`invalid.
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`B.
`60.
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`The Person of Ordinary Skill in the Art
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`I understand that patent validity is evaluated from the perspective of a
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`person of ordinary skill in the art (“POSA”) to which the patent pertains. I also
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`understand that Penn’s clinical expert, Dr. Frank M. Sacks, M.D., has proposed the
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`following definition for a person of ordinary skill in the art:
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`In March 2004 and 2005, the person of ordinary skill in the fields of
`the patent would have an M.D. and several years of experience in
`treating patients with lipid disorders, including hyperlipidemia and
`hypercholesterolemia. The person of ordinary skill in the art would
`also have had access to and worked [on a team] with a number of
`other individuals involved in drug discovery and development with
`advanced degrees in medicinal chemistry, pharmacology, or drug
`delivery sciences and having several years of experience in the
`development of drugs for the U.S. market.
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`19
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
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`61.
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`I agree with Dr. Sacks’ POSA definition. Although I do not hold an
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`M.D. degree, I believe my background, knowledge, and experience gives me
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`sufficient insight as to the perspective of a POSA. I have worked on cross-
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`disciplinary teams on drug discovery and the development of drugs for the U.S.
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`market.
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`62.
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`I have reviewed and also considered the issues using the alternative
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`definition of a POSA that CFAD’s experts, Drs. Mayersohn and Zusman, have
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`offered in each of their declarations. CFAD Ex. 1003 (Mayersohn Dec.) at ¶ 26;
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`CFAD Ex. 1002 (Zusman Dec.) at ¶¶ 27-32. My opinions in this case would not
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`change if the PTAB decides to adopt this POSA definition rather than that
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`proposed by Dr. Sacks.
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`63. Finally, I am aware that Dr. Zusman has explicitly mentioned the Pink
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`Sheet 2004 and Stein as references that a POSA would have reviewed in March
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`2004 or 2005. CFAD Ex. 1002 (Zusman Dec.) at ¶ 27. My opinions offered
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`below are not dependent on whether or not the Pink Sheet 2004 is within the
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`universe of documents considered by a POSA, as the claimed subject matter is not
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`obvious in view of those references, and I offer no opinion as to whether the POSA
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`would have had access to the Pink Sheet 2004 or Stein.
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`20
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`PENN EX. 2024
`CFAD v. PENN
`IPR2015-01836
`
`

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`C. Obviousness
`64.
`I have been informed by counsel that a claimed invention is obvious if
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`the claimed subject matter as a whole would have been obvious to a POSA prior to
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`the effective filing date of the patent at issue.
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`65.
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`I understand that the parties in this case dispute whether the effective
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`filing date for the patents-at-issue should be March 5, 2004 (the filing date of the
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`’915 provisional) or March 7, 2005 (the filing date of the ’268 patent). I am not
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`offering any opinion on this issue, and my analysis offered below would not
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`change regardless of which date applies.
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`66.
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`I understand that an obviousness analysis must be conducted from the
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`point of view of a POSA, not the inventor(s). Because inventors may have access
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`to proprietary information which a POSA would not, I understand that the specific
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`motivations and/or purposes of a patent’s inventor(s) can be irrelevant to a
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`determination of obviousness. Accordingly, I understand what is important is
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`whether there existed at the time of the invention a known problem for which the
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`prior art provided an obvious solution encompassed by the patent’s claims.
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`67.
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`I understand that an obviousness determination involves four factual
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`inquiries concerning: (1) the scope and content of the prior art; (2) the level of
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`21
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`PENN EX. 2024
`CF