UNITED STATES PATENT AND TRADEMARK OFFICE
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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 DANIEL A. BLOCH, PH.D.
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`1 Cases IPR2017-00578 and IPR2017-00596 have been joined with this
`proceeding.
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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 DANIEL A. BLOCH, PH.D.
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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
`
`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
`
`EX. 2015
`
`i
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`
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`EX. 2016
`
`EX. 2017
`EX. 2018
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`EX. 2019
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`EX. 2020
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`EX. 2021
`
`EX. 2022
`
`EX. 2023
`EX. 2024
`EX. 2025
`EX. 2026
`EX. 2027
`EX. 2028
`EX. 2029
`
`EX. 2030
`EX. 2031
`
`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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`
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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
`
`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
`
`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
`
`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 Dr. Daniel A. Bloch given on July 14, 2017
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`(Ex. 2083).
`
`Dr. Bloch’s Analysis of the Data in Sall Figure 2
`is Inaccurate and Scientifically Unsound
`
`In Ex. 2083 at p. 40, lines 4 to 8, p. 78, lines 13 to p. 79, line 16, and p. 88,
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`line 20 to p. 90, line 22, Dr. Bloch testified as follows:
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` (1) Dr. Bloch based his calculations off of “approximations” he gathered
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`from Sall Figure 2 using a magnifying glass and a ruler (40:4-8; 78:13-79:16);
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`(2) Dr. Bloch did not calculate the P values to confirm calculations based off
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`his “approximations” were consistent with the P values reported in Sall Figure 2
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`(89:6-90:22); and
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`(3) Dr. Bloch agreed the P values calculated using his “approximations” are
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`different than the P values reported by Sall (88:20-89:5).
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`Dr. Bloch’s deposition testimony is relevant to his statement at ¶ 47 of his
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`declaration (Ex. 1040) in which he states “the lack of statistically significant
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`difference between the cyclosporin formulation groups in Sall Figures 1 and 2
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`again tells us something very important—the two formulations performed the
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`same.” The deposition testimony is relevant because it demonstrates that Dr.
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`Bloch’s analysis from which he bases his conclusion was scientifically unsound
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`and inaccurate.
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`Dr. Bloch Failed to Review Clinical Evidence Demonstrating the 0.05% CsA
`Formulation Works Differently than the 0.1% CsA Formulation
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`In Ex. 2083 at p. 95, line 24 to p. 98, line 2 and p. 103, line 8 to 11, Dr.
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`Bloch admitted that he did not review any of the publicly available FDA files
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`related to the approval of RESTASIS® in preparing his declaration, including
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`Exhibit 2078. Dr. Bloch’s deposition testimony is relevant to his statements at ¶
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`35 of his declaration (Ex. 1040) where he states he has found no evidence of
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`statistically significant differences between the 0.05% and 0.1% formulations. The
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`deposition testimony is relevant because it demonstrates that Dr. Bloch’s analysis
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`from which he bases his conclusion that the 0.05% and 0.1% formulations
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`“performed the same” (see Ex. 2083 at p. 92 lines 9 to 15) did not include review
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`of documents submitted to the FDA, including Ex. 2078, which demonstrates the
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`FDA found statistically significant differences between the 0.05% formulation and
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`the 0.1% CsA formulation.
`
`Dr. Bloch’s Critiques of Dr. Attar’s Analyses Are Unnecessary and
`Unfounded
`
`In Ex. 2083 at p. 38, line 13 to p. 41 line 4, p. 52, lines 12 to 15 and p. 76,
`
`
`
`lines 7 to 20, Dr. Bloch testified as follows:
`
`(1)
`
`Dr. Bloch used a magnifying glass and ruler to draw lines
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`on Exhibit B to estimate the value of the bars on the chart (38:13-41:4);
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`Dr. Attar was not lying when she testified she used
`
`(2)
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`measurements from both the upper and lower conjunctiva to generate the
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`data in the right-most bar of Exhibit B (52:12-15); and
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`(3) whether Dr. Attar had used 0.29 versus 0.32 to generate the right-most
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`bar of Exhibit B “qualitatively it makes no difference” and “the point would have
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`been essentially identical” (76:7-20).
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`Dr. Bloch’s deposition testimony is relevant to:
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`(1) statements at ¶¶ 67 and 68 of his declaration (Ex. 1040) where he opined
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`about “Dr. Attar’s changing recollection”, Dr Attar’s inconsistent “amended
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`testimony that was elicited by Allergan’s counsel,” and Dr. Attar doing “the wrong
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`‘thing’ (analysis) when she created her Exhibit B.”
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` (2) statements at ¶ 68 of his declaration (Ex. 1040) where Dr. Bloch opines
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`that “it becomes clear that the value of the right-most bar in Exhibit B represents a
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`ratio of approximately 0.32 and not 0.29. This analysis indicates that the right-
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`most bar graph on Exhibit B represents the relative AUCs for lower conjunctiva
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`data in the 074 study, not the pooled conjunctiva data.”
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`Dr. Bloch’s deposition testimony is relevant because it proves that Dr.
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`Bloch’s critiques of Dr. Attar’s data are unfounded and irrelevant because the
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`conclusion drawn from the data would have been essentially identical whether or
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`not 0.29 or 0.32 was used in the graph. In other words, Dr. Attar’s conclusion that
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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`“the relative extent that cyclosporin was absorbed increased in the relevant ocular
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`tissues, here, the cornea and the conjunctiva, where the amount of oil present in the
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`formulation was decreased but the weight percentage of cyclosporin stayed the
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`same” would not have changed. Ex. 1004 at p. 226.
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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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`
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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 Daniel A.
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`Bloch, Ph.D. 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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`Case IPR2016-01128
`Attorney Docket No: 13351-0008IP2
`
`
`Gary J. Speier
`Mark D. Schuman
`Carlson, Caspers, Vandenburgh, Lindquist & Schuman, P.A.
`225 South Sixth Street, Suite 4200
`Minneapolis, Minnesota 55402
`
`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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