UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________________
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner
`
`v.
`
`JANSSEN ONCOLOGY, INC.,
`
`Patent Owner
`
`
`
`U.S. Patent No. 8,822,438 to Auerbach et al.
`Issue Date: September 2, 2014
`Title: Methods and Compositions for Treating Cancer
`
`
`Inter Partes Review No. IPR2016-01332
`
`
`
`DECLARATION OF IVAN T. HOFMANN, CPA/CFF, CLP
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`
`
`
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 1
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`I.
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`TABLE OF CONTENTS
`Introduction ......................................................................................................3
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`II. Qualifications ...................................................................................................4
`
`III. Case Background .............................................................................................8
`
`A.
`B.
`C.
`D.
`
`Prostate Cancer ......................................................................................8
`Zytiga (abiraterone acetate) .................................................................10
`The ’438 Patent ...................................................................................11
`Prosecution of the ’438 Patent ............................................................12
`
`
`IV. The Definitions of Commercial Success and Nexus Relative to Objective
`Indicia of Nonobviousness ............................................................................13
`
`V.
`
`The Performance of Zytiga Does Not Provide Objective Indicia of
`Nonobviousness of the ’438 Patent Due to the Existence of a Blocking Patent
` .......................................................................................................................14
`
`VI. The Performance of Zytiga Does Not Provide Objective Indicia of
`Nonobviousness of the ’438 Patent because There is No Nexus between the
`Performance of Zytiga and the Claims of the ’438 Patent ............................17
`
`VII. The Performance Metrics for Zytiga Presented During the Prosecution of the
`’438 Patent are Misleading and Incomplete ..................................................21
`
`
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`
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 2
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`I, Ivan T. Hofmann, hereby declare as follows.
`
`I.
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`Introduction
`
`1.
`
`I am over the age of eighteen and otherwise competent to make this
`
`declaration.
`
`2.
`
`I have been retained as an independent expert on behalf of MYLAN
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`PHARMACEUTICALS INCORPORATED (“Mylan” or “Petitioner”) for the above-
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`captioned inter partes review (“IPR”).
`
`3.
`
`I understand that this IPR involves U.S. Patent No. 8,822,438 (the
`
`“’438 Patent” or the “Patent-at-Issue”).1 MYL Ex. 1001. I understand that Alan H.
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`Auerbach and Arie S. Belldegrun are the named inventors and that, according to the
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`United States Patent and Trademark Office (“USPTO”) records, the ’438 Patent is
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`currently assigned to JANSSEN ONCOLOGY, INC. (“Janssen” or “Patent Owner”).
`
`MYL Ex. 1001.
`
`
`
` 1
`
` I understand that the Patent Trial and Appeal Board instituted trial in IPR2016-
`00286, captioned Amerigen Pharms. Ltd. (Petitioner) v. Janssen Oncology, Inc.
`(Patent Owner), on May 31, 2016. I also understand that in conjunction with the
`petition, Amerigen filed the declaration of DeForest McDuff dated December 4, 2015
`(the “McDuff Declaration”). I reviewed the McDuff Declaration in forming my
`opinions.
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 3
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`4. My company, Gleason IP, a division of Gleason & Associates, P.C.
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`(“Gleason”), has been retained by Perkins Coie LLP on behalf of Mylan to evaluate
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`aspects of commercial success, from an economic perspective, as it pertains to Zytiga
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`(abiraterone acetate) and the ’438 Patent. Gleason is being compensated for the work
`
`performed on this engagement based on the time incurred by me at a rate of $435 per
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`hour and by other Gleason personnel, working at my direction and under my
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`supervision, at rates ranging from $95 to $275 per hour. Our compensation is not
`
`affected by the outcome of this case.
`
`5.
`
`In formulating my opinions, I have considered all documents cited in this
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`declaration. I have included a list of these documents in Attachment A-1 to this
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`declaration. This declaration summarizes my current opinions, which are subject to
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`change depending upon additional information and/or analysis. I reserve the right to
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`supplement this declaration in response to any opinions of experts on behalf of the
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`Patent Owner and/or as additional information becomes available.
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`II. Qualifications
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`6.
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`I am a Managing Director at Gleason, which is an economic, accounting,
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`and financial consulting firm that provides services primarily in the areas of Valuation,
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`Litigation Support, Intellectual Property, Forensic Accounting and Financial
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 4
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`Reorganization. I am the leader of the Intellectual Property Practice. Prior to joining
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`Gleason, I worked for the global firm of Deloitte & Touche, LLP.
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`7.
`
`I graduated magna cum laude from the University of Notre Dame in 1994
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`with a Bachelor of Business Administration degree and a double major in Economics
`
`and Accounting. I am a Certified Public Accountant (“CPA”). I am also Certified in
`
`Financial Forensics (“CFF”). I am a member of the Licensing Executives Society
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`(“LES”) and have received my Certified Licensing Professional (“CLP”) designation,
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`which is granted by the LES to professionals with demonstrated knowledge and
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`experience in the areas of intellectual property and licensing. I have attended and
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`instructed numerous continuing education seminars since the completion of my formal
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`education and have been a speaker on numerous occasions on a variety of financial,
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`economic, accounting, and valuation topics. I have presented to various bar
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`associations and organizations on the issues of intellectual property, financial damages,
`
`valuation, financial statement analysis, and other topics.
`
`8.
`
`I have extensive knowledge and experience in the areas of economic and
`
`market analysis as it relates to litigation matters. My experience in intellectual property
`
`matters includes the valuation of intellectual property, analysis of objective indicia of
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`nonobviousness, market analysis involving product performance, the determination of
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`damages associated with patent infringement and other intellectual property (including
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 5
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`lost profits, disgorgement, and reasonable royalty, as applicable), consideration of
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`irreparable harm, analysis of Panduit Factors related to demand for patented features,
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`and market analysis of non-infringing alternatives. I have analyzed damages claims in
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`trademark infringement, false advertising, and other cases involving the Lanham Act.
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`I have experience in a broad range of industries, including pharmaceuticals,
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`manufacturing, technology, healthcare, communications, construction, extractive, and
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`other industries.
`
`9. My work experience
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`includes
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`litigation support and consulting
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`engagements with a variety of pharmaceutical and biologics companies. In my work
`
`in the pharmaceutical industry, I have performed financial and economic analysis for
`
`over one hundred prescription pharmaceutical products, including virtually every
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`major therapeutic class of drugs. I have been asked to study and analyze objective
`
`indicia of nonobviousness (including commercial success and nexus), consider claims
`
`of irreparable harm, determine and quantify damages, perform product pipeline
`
`consulting, and assist with licensing and settlement discussions.
`
`10.
`
`In the course of my work in providing consulting and expert services, I
`
`regularly analyze and review data for the pharmaceutical industry, including IMS
`
`Health Services, Inc. (“IMS”), Symphony Health Solutions, and other information
`
`service providers. I am knowledgeable regarding the role of pharmaceutical databases
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 6
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`such as First Databank, Medispan, Gold Standard, and other information sources in the
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`fulfillment of prescriptions. I am also knowledgeable regarding the process of
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`prescription writing, fulfillment, and generic substitution in the pharmaceutical
`
`industry. I have analyzed data and information and testified as an expert witness
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`numerous times in matters involving the pharmaceutical industry and the role of brand
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`versus generic competition. I have been qualified as an expert witness in
`
`pharmaceutical economics and specifically to address the issues of commercial success
`
`and nexus on numerous occasions by various federal courts and institutions.
`
`11.
`
`I have been engaged by the USPTO and Office of the Solicitor as an expert
`
`to analyze and testify on issues involving objective indicia of nonobviousness,
`
`including commercial success and nexus related to proceedings in which both the
`
`Honorable David Kappos, Under Secretary of Commerce for Intellectual Property and
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`former Director of the USPTO, and the Honorable Michelle Lee, in her official capacity
`
`as Under Secretary of Commerce for Intellectual Property and Director of the USPTO,
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`were defending the USPTO’s denial of certain patent applications.
`
`12.
`
`I also have extensive experience in analyzing, calculating, and
`
`determining damages and other financial and economic issues in various dispute
`
`settings. I have been designated as a testifying expert in federal and state courts,
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`Delaware Chancery Court, the United States International Trade Commission, and on
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 7
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`matters before various domestic and international arbitration panels. I have analyzed
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`damages involving intellectual property disputes, breach of contract claims,
`
`shareholder disputes, insurance recovery, class actions, and others. I also have
`
`experience assessing claims of irreparable harm in connection with temporary
`
`restraining order and preliminary injunction hearings, and determining whether
`
`financial damages are calculable. My full curriculum vitae is included as Attachment
`
`A-2.
`
`III. Case Background
`
`A.
`13.
`
`Prostate Cancer
`I understand that prostate cancer occurs in the male prostate, a small gland
`
`“that produces the seminal fluid that nourishes and transports sperm.”2 “Prostate cancer
`
`is one of the most common types of cancer in men,”3 with a one-in-seven lifetime risk
`
`
`
` 2
`
` I am not an oncologist or urologist. I cite my understandings to technical issues and
`various sources for those technical understandings as identified throughout this
`declaration. MYL Ex. 1051, Mayo Clinic Website, Prostate cancer,
`http://www.mayoclinic.org/diseases-conditions/prostate-
`cancer/basics/definition/con-20029597?p=1 (“Mayo Clinic”) (accessed 6/28/2016).
`3 MYL Ex. 1051 (Mayo Clinic).
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 8
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`of being diagnosed.4 In recent years, estimates for prostate cancer indicate nearly
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`181,000 new cases and more than 26,000 deaths annually in the U.S. alone.5
`
`14.
`
`I understand that patients diagnosed with prostate cancer may undergo a
`
`variety of treatment options, including: (1) active surveillance (i.e., no action taken until
`
`disease progresses); (2) radiation therapy (i.e., using “high-powered energy to kill
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`cancer cells”) and surgical removal of the prostate; (3) chemotherapy (i.e., using drugs
`
`to kill cancer cells); (4) hormone therapy (e.g., interrupting production of testosterone
`
`to kill or slow growth of cancer cells); and (5) other treatments such as cryosurgery
`
`(e.g., freezing tissue to kill cancer cells) and immunotherapy (e.g., genetically
`
`engineering immune cells to kill cancer cells).6
`
`15. Castrate-resistant prostate cancer (“CRPC”) refers to prostate cancer that
`
`is able to grow despite usage of treatments lowering androgen production.7 Metastatic
`
`castrate-resistant prostate cancer (“mCRPC”) refers to CRPC that has metastasized
`
`
`
` 4
`
` MYL Ex. 1041, Cancer.org (ACS), “What are the key statistics about prostate
`cancer?” http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-
`cancer-key-statistics (“ACS”) (accessed 6/28/2016).
`5 MYL Ex. 1041 (ACS).
`6 MYL Ex. 1051 (Mayo Clinic).
`7 MYL Ex. 1040, Cancer.net (ASCO Patient Website), Treatment of Metastatic
`Castration-Resistant Prostate Cancer, http://www.cancer.net/research-and-
`advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-
`castration-resistant-prostate-cancer (“ASCO”) (accessed 6/28/2016).
`
`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 9
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`beyond the prostate into other parts of the body.8 Studies have found that approximately
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`10 percent to 20 percent of patients with prostate cancer develop CRPC within five
`
`years of follow-up.9 Among these patients, at the time of CRPC diagnosis, at least 84
`
`percent would already have mCRPC, and of the remaining non-metastatic patients at
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`the time of diagnosis, 33 percent would develop mCRPC within two years.10
`
`B.
`Zytiga (abiraterone acetate)
`16. Zytiga (abiraterone acetate) is a CYP17 inhibitor indicated in combination
`
`with prednisone for the treatment of mCRPC.11 Zytiga works by interrupting androgen
`
`production (including, for example, testosterone) in the testes, adrenal glands, and
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`tumor.12 Zytiga is a type of hormone therapy.13
`
`17. Zytiga’s label indicates a recommended dose of 1,000 mg (via four 250-
`
`mg tablets) administered orally once-daily in combination with 5 mg prednisone
`
`
`
` 8
`
` MYL Ex. 1040 (ASCO).
`9 MYL Ex. 1050, Kirby, M., C. Hirst, and E.D. Crawford (2011), “Characterising the
`Castration-Resistant Prostate Cancer Population: A Systematic Review,” Int’l J.
`Clinical Practice 65(11):1180–1192, at 1180 (“Kirby”).
`10 MYL Ex. 1050 (Kirby) at 1180.
`11 MYL Ex. 1065, Zytiga Label, 5/20/2015, at 1.
`12 MYL Ex. 1066, Zytiga Website, How Zytiga® (abiraterone acetate) Works,
`https://www.zytiga.com/print/about-zytiga/how-zytiga-works (“Zytiga Website”)
`(accessed 6/28/2016).
`13 MYL Ex. 1051 (Mayo Clinic).
`MYL Ex. 1066 (Zytiga Website).
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 10
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`administered orally twice daily.14 The FDA initially approved Zytiga in April 2011
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`with an indication limited to patients whose prostate cancer progressed after treatment
`
`with docetaxel, a chemotherapy drug.15 In December 2012, the FDA approved Zytiga
`
`for treatment of patients with or without prior chemotherapy treatment.16
`
`C. The ’438 Patent
`18. The ’438 Patent, entitled “Methods and Compositions for Treating
`
`Cancer,” was filed on February 24, 2011, and issued on September 2, 2014.17 The
`
`abstract reads as follows:18
`
`Methods and compositions for treating cancer are described herein.
`More particularly, the methods for treating cancer comprise
`administering a 17α-hydroxylase/C17,20-lyase inhibitor, such as
`abiraterone acetate (i.e., 3β-acetoxy-17-(3-pyridyl)androsta-5,16-
`diene), in combination with at least one additional therapeutic agent
`such as an anti-cancer agent or a steroid. Furthermore, disclosed
`are compositions comprising a 17α-hydroxylase/C17,20-lyase
`inhibitor, and at least one additional therapeutic agent, such as an
`anti-cancer agent or a steroid.
`
`
`
`14 MYL Ex. 1065 (Zytiga Label) at 1.
`15 MYL Ex. 1046, FDA Website, Drugs@FDA – Zytiga,
`http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Searc
`h.DrugDetails (accessed 6/28/2016); MYL Ex. 1045, FDA News Release, “FDA
`expands Zytiga’s use for late-stage prostate cancer,” 12/10/2012,
`http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm331492.ht
`m (accessed 6/30/2016) (“FDA News Release”).
`16 MYL Ex. 1065 (Zytiga Label) at 1; MYL Ex. 1045 (FDA News Release).
`17 MYL Ex. 1001 (’438 patent).
`18 MYL Ex. 1001 (’438 patent).
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`19.
`
`Independent claim 1, the only independent claim, reads as follows: “A
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`method for the treatment of prostate cancer in a human comprising administering to said
`
`human a therapeutically effective amount of abiraterone acetate or a pharmaceutically
`
`acceptable salt thereof and a therapeutically effective amount of prednisone.”19
`
`D.
`20.
`
`Prosecution of the ’438 Patent
`I understand that the application from which the ’438 Patent issued was
`
`filed on February 24, 2011, and the ’438 Patent issued on September 2, 2014.20 During
`
`that period, I understand that Johnson & Johnson (“J&J”) and related parties
`
`corresponded with the USPTO regarding the patentability of the presented claims.21 In
`
`particular, I understand that the USPTO rejected the presented claims several times on
`
`the grounds of obviousness and double patenting, but ultimately allowed 20 claims
`
`based on “unexpected commercial success of the launch of the drug” and withdrawal of
`
`a co-pending patent application.22
`
`
`
`19 MYL Ex. 1001 (’438 patent).
`20 MYL Ex. 1001 (’438 patent).
`21 For brevity, I typically refer to these related entities, collectively, as J&J.
`22 MYL Ex. 1013 (’438 Patent Prosecution History July 3, 2013 Notice of
`Allowance) at 2–3; MYL Ex. 1039 (’438 Patent Prosecution History September 11,
`2012 Office Action) at 1–6.
`
`
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`IV. The Definitions of Commercial Success and Nexus Relative to Objective
`Indicia of Nonobviousness
`
`21.
`
`It is my understanding that “commercial success” is a legal construct that
`
`has been established through case law. Analysis of commercial success is premised on
`
`the concept that if a product is economically successful, it may provide objective
`
`evidence of nonobviousness.
`
`22.
`
`I also understand that courts have found that commercial success may not
`
`provide objective indicia of nonobviousness for asserted claims of patents where the
`
`underlying product (or in the case of pharmaceuticals, the underlying compound) is
`
`protected by a patent and/or regulatory exclusivity that prevents competition in the
`
`market. Similarly, I understand that the existence of blocking patents disincentivizes
`
`others from pursuing a solution to a market demand if the solution would infringe a
`
`blocking patent.
`
`23.
`
`I further understand that the commercial success of the product must be
`
`attributable to the alleged novel features of the claimed invention. I understand this to
`
`mean that, to support a finding of nonobviousness, any alleged commercial success
`
`requires that the success of the claimed product must have resulted from the merits of
`
`the claimed invention as opposed to the prior art or other extrinsic factors. In other
`
`words, there must be a causal correlation, or “nexus,” between the unique merit of the
`
`claimed invention and the success of the product. I also understand that if purported
`
`
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`commercial success is due to an element in the prior art, no nexus exists. In essence, I
`
`understand that if the feature that drives the purported commercial success was known
`
`in the prior art, such success is not pertinent.
`
`V. The Performance of Zytiga Does Not Provide Objective Indicia of
`Nonobviousness of the ’438 Patent Due to the Existence of a Blocking
`Patent
`
`24. The performance of Zytiga fails to provide objective indicia of
`
`nonobviousness of the claims of the ’438 Patent because no other company had an
`
`ability to commercialize a pharmaceutical product containing the compounds both
`
`before and after the filing date of the ’438 Patent because of patent exclusivities, as
`
`discussed below. A blocking patent is one that effectively blocks others from making,
`
`selling, or using a product without use of that patent.23
`
`25. U.S. Patent No. 5,604,213 (the “’213 Patent”), entitled “17-Substituted
`
`Steroids Useful in Cancer Treatment,” describes the abiraterone compound and
`
`methods for treating an androgen-dependent or estrogen-dependent disorder using that
`
`
`
`23 See, e.g., MYL Ex. 1054, Murphy et al. (2012), Patent Valuation: Improving
`Decision Making through Analysis, Wiley, at 102. (“A blocking patent is a patent
`that blocks a rights holder on a different patent from exploiting the different
`patented invention without a license to the blocking patent.”).
`
`
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`compound.24 According to the FDA’s Orange Book, a publication where companies
`
`list patents that are asserted to cover pharmaceutical products, the ’213 Patent has been
`
`alleged to cover Zytiga.25 The application from which the ’213 Patent issued was filed
`
`in 1994 and the ’213 Patent issued in 1997, long before the earliest filing date to which
`
`’438 Patent claims priority: the date of its provisional patent application filed in 2006.26
`
`According to the FDA, the ’213 Patent is expected to expire in December 2016.27
`
`26. The ’213 Patent is a blocking patent covering Zytiga and thus creates
`
`economic and legal barriers to commercially launching products containing abiraterone.
`
`This, in turn, creates a disincentive for potential competitors to research and develop
`
`abiraterone and the claimed ’438 Patent subject matter due to the inability to
`
`commercialize an abiraterone-containing product. From an economic perspective, the
`
`existence of a blocking patent that prevents others from making, selling, or using an
`
`abiraterone product would provide companies limited economic incentives to develop
`
`the invention claimed in the ’438 Patent.
`
`
`
`24 MYL Ex. 1005 (’213 patent); MYL Ex. 1036 (’438 Patent Prosecution History
`February 24, 2011 Initial Application) at 7, 10.
`25 MYL Ex. 1047, FDA Website, Orange Book, Zytiga (NDA 202379),
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_
`No=202379&Product_No=001&table1=OB_Rx (“Orange Book”) (accessed
`6/30/2016).
`26 MYL Ex. 1001 (’438 patent).
`27 MYL Ex. 1047 (Orange Book).
`
`
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`27.
`
`I understand that courts have found that, in the presence of blocking rights,
`
`existence of commercial success provides little probative value on whether a claimed
`
`technology is obvious.28
`
`
`
`28 MYL Ex. 1053, Merck & Co. v. Teva Pharms. USA, Inc., 395 F.3d 1364, 1376–77
`(Fed. Cir. 2005) (“Commercial success is relevant because the law presumes an
`idea would successfully have been brought to market sooner, in response to market
`forces, had the idea been obvious to persons skilled in the art….In this case Merck
`had a right to exclude others from practicing the weekly-dosing of alendronate
`specified in claims 23 and 37, given (1) another patent covering the administration
`of alendronate sodium to treat osteoporosis, U.S. Pat. No. 4,621,077 (issued Nov.
`4, 1986); and (2) its exclusive statutory right, in conjunction with FDA marketing
`approvals, to offer Fosamax at any dosage for the next five years. Because market
`entry by others was precluded on those bases, the inference of non-obviousness of
`weekly-dosing, from evidence of commercial success, is weak.”); MYL Ex. 1057,
`Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1383 (Fed. Cir. 2005) (“[A]
`high degree of commercial success permits the inference that others have tried and
`failed to reach a solution. In Merck, we held that evidence of commercial success
`resulted in a particularly weak inference because prior art patents prevented others
`from competing to reach the solution embodied in the claims at issue.”); MYL Ex.
`1048, Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d 731, 740–41 (Fed. Cir. 2013)
`(“Where ‘market entry by others was precluded [due to blocking patents], the
`inference of non-obviousness of [the asserted claims], from evidence of
`commercial success, is weak.’ This principle applies forcefully to the present case.
`The now expired Shroot patents blocked the market entry of 0.3% adapalene
`products until their expiration in 2010, long after Galderma invented 0.3%
`adapalene compositions of the asserted claims. As such, no entity other than
`Galderma could have successfully brought to 0.3% to market prior to 2010. Like
`the commercial success described in Merck & Co., the commercial success of
`Differin® Gel, 0.3% is of ‘minimal probative value.’”).
`
`
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`28. Based on my analysis from an economic perspective, the existence of the
`
`’213 Patent prevents the performance of Zytiga from providing objective evidence of
`
`nonobviousness of the ’438 Patent.
`
`VI. The Performance of Zytiga Does Not Provide Objective Indicia of
`Nonobviousness of the ’438 Patent because There is No Nexus between the
`Performance of Zytiga and the Claims of the ’438 Patent
`
`29. As explained above, commercial success is only informative on
`
`nonobviousness of a particular invention if there is a demonstrated nexus between that
`
`purported success and the alleged invention. However, I am not aware of any evidence
`
`provided during patent prosecution regarding nexus to the ’438 Patent and the
`
`performance of Zytiga. By contrast, several factors indicate a lack of nexus between
`
`the alleged invention claimed in the ’438 Patent and the performance of Zytiga.
`
`30. As explained below, the performance of Zytiga can be attributed to factors
`
`that I understand are not claimed by the ’438 Patent and were previously known.
`
`Specifically, I understand the claims of the ’438 Patent do not cover (1) the individual
`
`compounds abiraterone acetate or prednisone or (2) the method using combinations of
`
`drugs for the treatment of patients with prostate cancer. As a result, there is no evidence
`
`that Zytiga sales are due to the benefits of the combination of abiraterone and
`
`prednisone, rather than the sum of the benefits of each component individually.
`
`Furthermore, I understand that the use of the specific glucocorticoid prednisone has not
`
`
`
`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 17
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`been shown to have incremental benefit over other glucocorticoid steroids, which I
`
`understand are not covered by the ’438 Patent.29
`
`31. As discussed above, I understand that the compound that is the active
`
`ingredient in Zytiga, abiraterone acetate, is alleged to be covered by the ’213 Patent, not
`
`the ’438 Patent.30 I understand that during patent prosecution, J&J provided no
`
`evidence or meaningful analysis indicating that any alleged success was due to
`
`contribution of the technology claimed in the ’438 Patent versus the ’213 Patent.
`
`32. Furthermore, I understand from Dr. Garnick’s Declaration that the
`
`methods of treating patients with combinations of drugs are known and common in the
`
`marketplace for cancer treatment. For example, I understand that other CYP17
`
`inhibitors, such as ketoconazole, were previously used to treat prostate cancer before
`
`abiraterone acetate and that it was standard practice to co-administer hydrocortisone or
`
`prednisone with ketoconazole to address common side effects like hypertension,
`
`hypokalemia, and fluid retention.31 Similarly, dosing information for Jevtana
`
`(cabazitaxel; approved before J&J filed the NDA for Zytiga), a chemotherapy drug
`
`
`
`29 MYL Ex. 1002 (Declaration of Marc B. Garnick, M.D. (“Garnick Decl.”)) ¶ 79.
`30 MYL Ex. 1047 (Orange Book).
`31 MYL Ex. 1002 (Garnick Decl.) ¶¶ 33, 42; MYL Ex. 1064 (Zytiga Brochure,
`Putting Prednisone in Perspective, 3/2015).
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`administered to cancer patients, is indicated with concurrent administration of
`
`prednisone.32
`
`33. Given the ’438 Patent does not claim the compounds or the general
`
`methods of treating patients with combinations of drugs, there is no evidence that the
`
`performance of Zytiga is due to the benefits of the combination of abiraterone and
`
`prednisone. For example, the USPTO examiner indicated that abiraterone and
`
`prednisone were known to be individually effective for the treatment of prostate
`
`cancer.33 Yet J&J did not assert during patent prosecution that the performance of
`
`Zytiga was attributable to purported benefits of the combination beyond the known
`
`benefits of each treatment. I understand that Dr. Garnick is of the opinion that there are
`
`“no unexpected anti-cancer synergies resulting from co-administering abiraterone and
`
`prednisone” and that the sales of Zytiga are not the result of any unexpected synergies.34
`
`34. Furthermore, I understand that the use of the specific glucocorticoid
`
`prednisone has not been shown to have incremental benefit over other glucocorticoid
`
`steroids. I understand from Dr. Garnick’s declaration that, from a clinical perspective,
`
`
`
`32 MYL Ex. 1049, Jevtana Website, Dosing and Administration,
`http://www.jevtana.com/hcp/dosing/default.aspx (accessed 6/28/2016).
`33 MYL Ex. 1011(’438 Patent Prosecution History, March 4, 2013 Office Action) at
`1–6.
`34 MYL Ex. 1002 (Garnick Decl.) ¶¶ 92-93.
`
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 19
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`the use of another glucocorticoid such as hydrocortisone, rather than prednisone, would
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`be expected to be just as effective as prednisone in enhancing the tolerability of
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`abiraterone administration.35 I further understand that, from a medical perspective,
`
`treatments combining prednisone with other drugs have been known to be effective, and
`
`that the additional benefit from the combination has not been tested, but is not expected
`
`to result in any significant enhancement of anti-cancer effects.36 Since no studies have
`
`compared the administration of abiraterone acetate plus prednisone with the
`
`administration of abiraterone acetate alone, the addition of prednisone (i.e., the alleged
`
`incremental contribution of the ’438 Patent over the ’213 Patent) has not been shown to
`
`have any additional benefit beyond increasing the tolerability of the treatment, which
`
`was already a known benefit of prednisone.37 Similarly, during prosecution of the ’438
`
`Patent, the USPTO examiner determined that the alleged presence of “unexpected
`
`results because abiraterone plus prednisone being more effective than prednisone alone”
`
`was fully considered and found unpersuasive in originally denying J&J’s patent
`
`application.38
`
`
`
`35 MYL Ex. 1002 (Garnick Decl.) ¶¶ 79-80.
`36 MYL Ex. 1002 (Garnick Decl.) ¶¶ 78-79, 83, and 92.
`37 MYL Ex. 1002 (Garnick Decl.) ¶¶ 78-79, 83, and 92.
`38 MYL Ex. 1011 (’438 Patent Prosecution History, March 4, 2013 Office Action) at
`1–6.
`
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`MYLAN PHARMS. INC. EXHIBIT 1017 PAGE 20
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`VII. The Performance Metrics for Zytiga Presented During the Prosecution of
`the ’438 Patent are Misleading and Incomplete
`
`35. As explained above, the USPTO cited “unexpected commercial success of
`
`the launch of the drug” as a basis for nonobviousness in granting the ’438 Patent. Based
`
`upon documents at the time of the prosecution, the USPTO was presented with
`
`information about the commercial performance of Zytiga on a patient-share basis and
`
`relative to other oral cancer drugs. The information provided to the USPTO was
`
`misleading and incomplete for the reasons I describe below.
`
`36.
`
`I am not aware of J&J providing the USPTO with any expectations or
`
`perceptions of expected commercial success of Zytiga by the broader market prior to
`
`launch. Instead, J&J relied exclusively on measures of actual Zytiga sales, including
`
`arguments based on early sales as of 2012 that were rejected by the USPTO39 and
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`arguments based on sales to date through April 2013.40 Without a baseline for
`
`expectations, the term “unexpected” is misplaced.
`
`37. An example of the misleading and incomplete performance metrics
`
`presented during patent prosecution is the information regarding Zytiga’s “almost 70%
`
`
`
`39 MYL Ex. 1008 (’438 Patent Prosecution History, July 3, 2012 Response) at 1–4;
`MYL Ex. 1039 (’438 Patent Prosecution History, September 11, 2012 Office
`Action) at 1–6.
`40 MYL Ex. 1012 (’438 Patent Prosecution History June 4, 2013 Response) at 7–8.
`
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`market share,” and Zytiga’s “market lead[ing]” position for post-chem