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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`MYLAN PHARMACEUTICALS INC.,
`Petitioner
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`v.
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`ALLERGAN, INC.
`Patent Owner
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`Case IPR2016-011281
`Patent 8,629,111
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`PATENT OWNER ALLERGAN’S MOTION
`FOR OBSERVATIONS ON THE CROSS-EXAMINATION
`TESTIMONY OF IVAN T. HOFMANN
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`
`1 Cases IPR2017-00578 and IPR2017-00596 have been joined with this
`proceeding.
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`
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`
`EXHIBIT LIST
`
`EX. 2002
`EX. 2003
`
`EX. 2004
`EX. 2005
`EX. 2006
`EX. 2007
`EX. 2008
`EX. 2009
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`EX. 2010
`EX. 2011
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`EX. 2012
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`EX. 2013
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`Exhibit No. Description
`EX. 2001
`NDA 21-023 Cyclosporine Ophthalmic Emulsion 0.05%, Original
`NDA Filing, Vol. 1 (Feb. 24, 1999)
`U.S. Pat. No. 4,839,342
`Said et al., Investigative Ophthalmology & Visual Science, vol. 48,
`No. 11 (Nov. 2007):5000-5006
`Alba et al., Folia Ophthalmol. Jpn. 40:902-908 (1989)
`Stedman’s Medical Dictionary, definition of therapeutic
`Dorland’s Illustrated Medical Dictionary, definition of therapeutic
`Stedman’s Medical Dictionary, definition of palliative
`RESTASIS® label
`Murphy, R., “The Once and Future Treatment of Dry Eye,” Review
`of Optometry, pp. 73-75 (Feb. 15, 2000)
`RESERVED
`Agarwal, Priyanka and Ilva D. Rupenthal, “Modern Approaches to
`the Ocular Delivery of Cyclosporine A,” Drug Discovery Today,
`vol. 21, no. 6 (June 2016)
`Damato et al., “Senile Atrophy of the Human Lacrimal Gland: The
`Contribution of Chronic Inflammatory Disease,” British Journal of
`Ophthalmology (1984)
`Higuchi, “Physical Chemical Analysis of Percutaneous Absorption
`Process From Creams and Ointments,” Seminar, New York City
`(1959)
`Lallemand et al., “Cyclosporine a Delivery to the Eye: A
`Pharmaceutical Challenge,” European Journal of Pharmaceutics
`and Biopharmaceutics (2003)
`das Neves et al., “ Mucosal Delivery of Biopharmaceuticals:
`
`EX. 2014
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`EX. 2015
`
`i
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`
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`EX. 2016
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`EX. 2017
`EX. 2018
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`EX. 2019
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`EX. 2020
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`EX. 2021
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`EX. 2022
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`EX. 2023
`EX. 2024
`EX. 2025
`EX. 2026
`EX. 2027
`EX. 2028
`EX. 2029
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`EX. 2030
`EX. 2031
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`Biology, Challenges and Strategies,” Springer Science (2014)
`Power et al., “Effect of Topical Cyclosporin A on Conjunctival T
`Cells in Patients with Secondary Sjögren’s Syndrome,” Cornea
`12(6): 507-511 (1993)
`Schaefer et al., “Skin Permeability,” Springer-Verlag (1982)
`Stern et al., “The Pathology of Dry Eye: The Interaction Between
`the Ocular Surface and Lacrimal Glands,” Cornea 17(6): 584-589
`(1998)
`Wepierre, Jacques and Jean-Paul Marty, “Percutaneous Absorption
`of Drugs,” Elsvier/North-Holland Biomedical Press (1970)
`Williamson et al., “Histology f the Lacrimal Gland in
`Keratoconjunctivitis Sicca,” Brit. F. Ophthal /91973)
`“Approved Drug Products with Therapeutic Equivalence
`Evaluations,” U.S. Department of Health and Huma Services, 37th
`Edition (2017)
`Lemp, Michael A., “ Report of the National Eye Institute/Industry
`Workshop on Clinical Trials in Dry Eyes,” CLAO Journal, vol. 21,
`no. 4 (October 1995)
`Deposition transcript of Mansoor Amiji, Ph.D
`Declaration of John D. Sheppard, M.D., M.M.Sc.
`Declaration of Dr. Thorsteinn Loftsson, Ph.D.
`Declaration of Eric Rubinson
`Allergan PK-98-074 Report
`Declaration of Robert S. Maness, Ph.D.
`DiMasi, “Risks in New Drug Development: Approval Success
`Rates for Investigational Drugs,” Clinical Pharmacology and
`Therapeutics, May 2001
`FDA Review, “The Drug Development and Approval Process”
`Allergan – NYSE: AGN – Company Profile
`
`ii
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`EX. 2032
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`EX. 2033
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`EX. 2034
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`EX. 2035
`EX. 2036
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`EX. 2037
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`EX. 2038
`EX. 2039
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`EX. 2040
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`EX. 2041
`EX. 2042
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`EX. 2043
`EX. 2044
`EX. 2045
`EX. 2046
`EX. 2047
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`EX. 2048
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`Drugs@FDA: FDA Approved Drug Products,
`http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=ov
`erview.process&ApplNo=021023
`Drugs@FDA: FDA Approved Drug Products, Restasis Approved,
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-
`023_Restasis_Approv.PDF
`Drugs@FDA: FDA Approved Drug Products,
`http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=ov
`erview.process&ApplNo=050790
`Facts About Dry Eye, https://nei.nih.gov/health/dryeye/dryeye
`Christopher Glenn, “New Thinking Spurs New Products,” Review
`of Ophthalmology, February 15, 2003
`Mark B. Abelson, MD and Jason Casavant, “Give Dry Eye a One-
`two Punch,” Review of Ophthalmology, March 15, 2003
`Deposition of David LeCause, February 17, 2017
`Joan-Marie Stiglich ELS, “Restasis: the road to approval,” Ocular
`Surgery News, March 1, 2003
`Lynda Charters, “Increased Tear Production,” Ophthalmology
`Times, February 1, 2003
`RESERVED
`Jonathan R. Pirnazar, MD, “Taking a Custom Approach to Dry Eye
`Treatment,” Ophthalmology Management, February 1, 2004
`RESERVED
`FDA label for Xiidra®
`RESERVED
`Restasis Strategic Plan Forecast 2009-2013
`Allergan Inc., Credit Suisse First Boston Equity Research Report,
`Jan 30, 2003
`Allergan Inc., Buckingham Research Group Equity Research
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`iii
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`
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`EX. 2049
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`EX. 2050
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`EX. 2051
`EX. 2052
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`EX. 2053
`EX. 2054
`EX. 2055
`EX. 2056
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`EX. 2057
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`EX. 2058
`EX. 2059
`EX. 2060
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`EX. 2061
`EX. 2062
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`EX. 2063
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`EX. 2064
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`EX. 2065
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
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`Report, Feb 5, 2003
`Allergan Inc., SalomonSmithBarney Equity Research Report, Feb
`12, 2003
`Allergan Inc., Morgan Stanley Equity Research Report, Jan 30,
`2003
`Restasis P&L (US Only excl. Canada and Puerto Rico)
`Allergan Inc., Morgan Stanley Equity Research Report, Apr 30,
`2004
`Allergan Inc., JP Morgan Equity Research Report, Nov 1, 2005
`RESERVED
`“commercial Restasis Formulary June 2006.xls”
`“NOVEMBER 2006 input MHC Report Restasis Playbook
`data.ppt”
`Restasis® 2013 Managed Markets Tactics & Preliminary Budget,
`August 8, 2012
`RESERVED
`RESERVED
`“Allergan Inc. (AGN) - Q4 2002 Financial Release Conference Call
`Wednesday, January 29, 2003 11:00 am” Fair Disclosure Financial
`Network
`Restasis Launch Marketing Plan, dated February 12-13, 2003
`Allergan Dry Eye, “Dry Eye Franchise 2014 Business Plan,” 2014
`U.S. Eye Care Sales & Marketing Plan, September 9, 2013
`Allergan Eye Care, “US Dry Eye Strat Plan Narrative: Summary
`Version,” April 16, 2011
`Kline, Kate, “Restasis Professional Critical Issues,” Allergan Dry
`Eye, 2010
`Allergan Dry Eye, “Restasis Business Update,” August 16, 2010
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`iv
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`EX. 2066
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`EX. 2067
`EX. 2068
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`EX. 2069
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`EX. 2070
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`EX. 2071
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`EX. 2072
`EX. 2073
`EX. 2074
`EX. 2075
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`EX. 2076
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`EX. 2077
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`EX. 2078
`EX. 2079
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`EX. 2080
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`“Sales-Units_2011-2016_AllData_NSP_Feb-19-
`2017_RESTASIS.xlsx”
`RESERVED
`Iazuka and Jin, “The Effect of Prescription Drug Advertising on
`Doctor Visits,” Journal of Economics and Management Strategy,
`2007
`Bradford, Kleit, Nietert, et al, “How Direct-to-Consumer Television
`Advertising for Osteoarthritis Drugs Affect Physicians’ Prescribing
`Behavior,” Health Affairs, 2006
`Calfee, Winston, and Stempski, “Direct-to-Consumer Advertising
`and the Demand for Cholesterol Reducing Drugs,” Journal of Law
`and Economics, 2002
`Bradford, Kleit, Nietert, et al, “Effects of Direct-to-Consumer
`Advertising of Hydroxymethylglutaryl Coenzyme A Reductase
`Inhibitors or Attainment of LDL-C Goals,” Clinical Therapeutics,
`2006
`Restasis NPA Monthly
`Restasis Projects, Global R&D Cost
`Refresh Endura Lubricant Eye Drops (Allergan), Theodora
`Declaration of Jonathan Singer in support of Petitioner’s Motion for
`Pro Hac Vice Admission
`Memorandum Opinion and Order, Allergan, Inc. v. Teva
`Pharmaceuticals USA, Inc., et al., Case No. 2:15-cv-1455-WCB
`Nussenblatt, R. et al. Local Cyclosporine Therapy for Experimental
`Autoimmune Uveitis in Rats. Arch Ophthalmology, Volume 103,
`October 1985.
`Medical Officer’s Review of NDA 21-023
`Correction to Sall article (Ex. 1007), Opthalmology, Vol. 107, No.
`7, July 2000.
`GraphPad Calculation of Bloch Table 2 – 3 mo. B vs A.
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`v
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`GraphPad Calculation of Bloch Table 2 – 3 mo. C vs A.
`Deposition transcript of Andrew F. Calman, M.D., Ph.D.
`Deposition transcript of Daniel A. Bloch, Ph.D.
`Deposition transcript of Ivan T. Hofmann
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`EX. 2081
`EX. 2082
`EX. 2083
`EX. 2084
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`vi
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`Patent Owner Allergan hereby submits observations on the deposition
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`testimony of Petitioner’s Declarant Mr. Ivan T. Hofmann given on July 14, 2017
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`(Ex. 2084).
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`Mr. Hofmann Does Not Dispute That Restasis® is a Commercial Success
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`In Ex. 2084 at p. 8, lines 22 to 25, Mr. Hofmann admitted that Restasis® has
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`experienced significant sales and profits, indicating that it is a commercial success.
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`Mr. Hofmann’s testimony is relevant to his statement in ¶ 29 of his declaration
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`(Ex. 1041) where he states that he “ha[s] not seen evidence demonstrating that the
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`claimed commercial success of Restasis® is attributable to novel features of the
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`alleged inventions of the Patents-at-Issue.” Mr. Hofmann’s deposition testimony is
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`relevant because it demonstrates that his dispute with Allergan’s claim of
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`commercial success is premised solely on establishing the nexus between the
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`claimed invention and Restasis®, not on whether Restasis® itself was
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`commercially successful.
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`Mr. Hofmann Fails to Define a Relevant Market After
`Incorrectly Criticizing Dr. Maness for the Same
`In Ex. 2084 at p. 17 lines 5 to 19, Mr. Hofmann acknowledges that Dr.
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`Maness provided a definition for a relevant market in his declaration. Mr.
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`Hofmann also acknowledges that he did not define the relevant market in his
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`testimony. See Ex. 2084 at p. 18 lines 2-17 (“I haven’t done a definitive definition
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`of which products would comprise the relevant market.”). Mr. Hofmann’s
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`testimony is relevant to his statement in ¶ 28 of his declaration (Ex. 1041) that
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`“sales must be considered in light of the relevant market” and in ¶ 42 that “[t]he
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`Maness Declaration is incomplete and flawed because it fails to provide the
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`appropriate context to the performance of Restasis® in the relevant market”. The
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`deposition testimony is relevant because it demonstrates that, by his own standard,
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`Mr. Hofmann’s analysis is flawed, as he did not analyze the relevant market in
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`which the sales took place.
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`Mr. Hofmann Does Not Dispute That Mere Presence of Product
`Marketing Does Not Indicate Lack of Nexus
`In Ex. 2084 at p. 47, line 25 to p. 48 line 6, Mr. Hofmann agrees that the
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`mere fact that a product is marketed does not mean there is a lack of nexus
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`between the commercial performance of a product and the patented invention.
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`Further, in Ex. 2084 at p. 48 lines 7-12, Mr. Hofmann admits that he did not
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`quantify how much marketing spend he considers excessive. Mr. Hofmann’s
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`testimony is relevant to his statement in ¶ 70 of his declaration (Ex. 1041) that “the
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`fact that Allergan has had to invest so heavily in sales and marketing efforts for
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`Restasis® undermines the Maness Declaration’s contention that a nexus exists
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`between the commercial performance of Restasis® and the claims of the Patents-
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`at-Issue.” The deposition testimony is relevant because it demonstrates that
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`marketing itself is not conclusive proof of lack of nexus, and that Mr. Hofmann did
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`not quantify about how much marketing is excessive.
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`Attorney Docket No: 13351-0008IP2
`Mr. Hofmann Fails to Credit Marketing as a Percentage of Sales
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`In Ex. 2084 at p. 36 line 11 to p. 37 line 7, Mr. Hofmann testified that he
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`does not consider marketing as a percentage of sales to be relevant to the role that
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`marketing plays in driving the commercial success of Restasis®. He does not
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`argue that Dr. Maness’s calculations are erroneous (see Ex. 2084 at p. 44 lines 9 to
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`15, where he agrees “the math checks out”), but argues that the metric “diminishes
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`the marketing intensity,” or in other words, downplays Allergan’s marketing
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`efforts. Mr. Hofmann’s deposition testimony is relevant to his statements at ¶¶ 63-
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`64 of his declaration (Ex. 1041) where he discusses the purported effect of
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`advertising and promotion on the commercial success of Restasis®. Mr.
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`Hofmann’s testimony is relevant because it demonstrates that he has not taken into
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`account the marketing expenses in the broader context of Restasis® sales in
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`assessing the commercial success of Restasis®.
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`Mr. Hofmann Fails to Compare Expenditures to Other Products
`in the Industry
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`In Ex. 2084 at p. 41 line 5 to p. 42 line 2, Mr. Hofmann admits that he does
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`not compare the sales and marketing expenses of Restasis® compared to other
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`pharmaceutical products with sales levels similar to Restasis®. See also Ex. 2084
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`p. 38 line 1 to p. 39 line 5. Mr. Hofmann’s testimony is relevant to ¶¶ 69-70 of his
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`declaration (Ex. 1041) where he sets forth the total sales and marketing expenses
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`of Restasis® from launch through 2016, and comments that “if the features of the
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`claims of the Patents-at-Issue were as novel and important as the Maness
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`Declaration implies, Allergan would not have needed to engage in the degree of
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`such extensive, prolonged, and continued marketing efforts as described below.”
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`Mr. Hofmann’s testimony is relevant because, without a comparison of Allergan’s
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`marketing efforts for Restasis® to the “continued marketing efforts” of other
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`pharmaceutical products with similar net sales, his assertion that such extensive
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`marketing would not have been required lacks context and support.
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`Mr. Hofmann Fails to Conduct an Apportionment Analysis
`After Criticizing Dr. Maness for the Same
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`In Ex. 2084 at p. 84 line 17 to p. 85 line 7, Mr. Hofmann criticizes Dr.
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`Maness for not apportioning the Restasis® sales and revenues across the prior art
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`patents and across the individual patents-in-suit. Mr. Hofmann acknowledges that
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`Dr. Maness considered apportionment (see Ex. 1034 at 250:10-251:9, 251:24-
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`252:21) and determined that it was inappropriate. Ex. 2084 at p. 85 lines 8-23.
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`Mr. Hofmann further admits that he never performed a quantitative apportionment
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`analysis, either across the alleged prior art patents (Ex. 2084 at p. 87 line 15 to p.
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`88 line 21) or across the individual patents-in-suit (Ex. 2084 at p. 85 line 24 to p.
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`86 line 17). See also Ex. 2084 at p. 89 lines 3 to 10. Mr. Hofmann’s testimony is
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`relevant to his statement in ¶ 105 of his declaration (Ex. 1041) that “[t]he failure to
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`apportion the sales and identify nexus to the Patents-at-Issue individually, as well
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`as other drivers of the performance of Restasis®, such as the ’979 Patent and ’342
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`Patent, is incomplete, flawed and unreliable.” The deposition testimony is relevant
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`because it demonstrates that again, by his own standard, Mr. Hofmann’s analysis is
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`flawed.
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`Mr. Hofmann Is Not Qualified to Interpret Scope of Patent Claims
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`In Ex. 2084 at p. 14, lines 5 to 8, Mr. Hofmann admitted that he is not an
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`expert in interpreting patent claims related to clinical features of pharmaceutical
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`formulations. Additionally, he testified at p. 99 lines 19 to 23, that “to determine
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`whether a patent is a blocking patent, you have to determine the scope of the
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`claims.” Ex. 2084; see also id. at p. 80 line 20 to p. 81 line 6. Mr. Hofmann’s
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`deposition testimony is relevant to his statements in ¶ 31 of his declaration (Ex.
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`1041) where he interprets the scope of the Ding ’979 patent to encompass
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`Restasis®, and is further relevant to his opinions at ¶¶ 30-38 regarding which
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`patents served as blocking patents, as well as the purported effect these “blocking
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`patents” had on the competitive market for Restasis®. Mr. Hofmann does not cite
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`to any of Petitioner’s technical experts for his interpretation of the scope of the
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`Ding ’979 patent in ¶ 31. See Ex. 1041 at FN 55; Ex. 2084 at p. 66 line 21 to p. 67
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`line 17. His testimony is relevant because any conclusions Mr. Hofmann draws
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`about certain patents acting as blocking patents stem from his own interpretation of
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`the scope of the patent claims, for which he admits he is not qualified to offer an
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`opinion.
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
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`Respectfully submitted,
`
`
`/Dorothy P. Whelan/
`Dorothy P. Whelan, Reg. No. 33,814
`Michael J. Kane, Reg. No. 39,722
`Attorneys for Allergan, Inc.
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`Date:/July 20, 2017/
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`Customer Number 26191
`Fish & Richardson P.C.
`Telephone: (612) 337-2509
`Facsimile: (612) 288-9696
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`CERTIFICATE OF SERVICE
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`Pursuant to 37 CFR §§ 42.6(e)(4) and 42.205(b), the undersigned certifies
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`that on July 20, 2017, a complete and entire copy of this Patent Owner Allergan,
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`Inc.’s Motion for Observations On the Cross-Examination Testimony of Ivan T.
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`Hofmann was provided via electronic service, to the Petitioner by serving the
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`correspondence address of record as follows:
`
`Steven W. Parmelee
`Michael T. Rosato
`Jad A. Mills
`Wendy L. Devine
`Wilson Sonsini Goodrich & Rosati
`701 Fifth Avenue, Suite 5100
`Seattle, WA 98104-7036
`sparmelee@wsgr.com
`mrosato@wsgr.com
`jmills@wsgr.com
`wdevine@wsgr.com
`
`
`Michael R. Dzwonczyk
`Azy S. Kokabi
`Travis B. Ribar
`Sughrue Mion, PLLC
`2100 Pennsylvania Ave., NW, Suite 800
`Washington, DC 20037
`mdzwonczyk@sughrue.com
`akokabi@sughrue.com
`tribar@sughrue.com
`sblackston@sughrue.com
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`
`Gary J. Speier
`Mark D. Schuman
`Carlson, Caspers, Vandenburgh, Lindquist & Schuman, P.A.
`225 South Sixth Street, Suite 4200
`Minneapolis, Minnesota 55402
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`gspeier@carlsoncaspers.com
`mschuman@carlsoncaspers.com
`IPRCyclosporine@carlsoncaspers.com
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` /Jessica K. Detko/
`
`Jessica K. Detko
`Fish & Richardson P.C.
`60 South Sixth Street, Suite 3200
`Minneapolis, MN 55402
`(612) 337-2516
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