`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`MYLAN PHARMACEUTICALS INC., TEVA PHARMACEUTICALS
`USA, INC., and AKORN INC.,
`Petitioners
`
`v.
`
`ALLERGAN, INC.
`Patent Owner
`
`
`
`
`
`
`
`
`
`
`Case IPR2016-011281
`Patent 8,629,111
`
`
`
`
`
`
`
`
`
`
`
`PATENT OWNER ALLERGAN, INC.’S
`OPPOSITION TO MOTION FOR DISCOVERY
`
`
`
`
`1 Cases IPR2017-00578 and IPR2017-00596 have been joined with this
`proceeding.
`
`
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`TABLE OF CONTENTS
`
`
`INTRODUCTION ............................................................................................ 1
`I.
`II. BACKGROUND .............................................................................................. 2
`III. LEGAL STANDARD ....................................................................................... 4
`IV. ARGUMENT .................................................................................................... 5
`A. The Motion Fails To Show The Requested Discovery Will Uncover
`Anything Useful ............................................................................................... 5
`B. Petitioner’s Reliance On Corning Is Misplaced ......................................... 6
`V. CONCULSION ................................................................................................. 7
`
`
`
`i
`
`
`
`
`
`
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`EXHIBITS
`
`EX. 2002
`EX. 2003
`
`EX. 2004
`EX. 2005
`EX. 2006
`EX. 2007
`EX. 2008
`EX. 2009
`
`EX. 2010
`EX. 2011
`
`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)
`
`EX. 2012
`
`EX. 2013
`
`EX. 2014
`
`ii
`
`
`
`
`
`EX. 2015
`
`EX. 2016
`
`EX. 2017
`EX. 2018
`
`EX. 2019
`
`EX. 2020
`
`EX. 2021
`
`EX. 2022
`
`EX. 2023
`EX. 2024
`EX. 2025
`EX. 2026
`EX. 2027
`EX. 2028
`EX. 2029
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`das Neves et al., “ Mucosal Delivery of Biopharmaceuticals:
`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
`
`iii
`
`
`
`
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`FDA Review, “The Drug Development and Approval Process”
`Allergan – NYSE: AGN – Company Profile
`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
`
`EX. 2030
`EX. 2031
`EX. 2032
`
`EX. 2033
`
`EX. 2034
`
`EX. 2035
`EX. 2036
`
`EX. 2037
`
`EX. 2038
`EX. 2039
`
`EX. 2040
`
`EX. 2041
`EX. 2042
`
`EX. 2043
`EX. 2044
`EX. 2045
`
`iv
`
`
`
`
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`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
`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
`
`EX. 2046
`EX. 2047
`
`EX. 2048
`
`EX. 2049
`
`EX. 2050
`
`EX. 2051
`EX. 2052
`
`EX. 2053
`EX. 2054
`EX. 2055
`EX. 2056
`
`EX. 2057
`
`EX. 2058
`EX. 2059
`EX. 2060
`
`EX. 2061
`EX. 2062
`
`v
`
`
`
`
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`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
`“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
`
`EX. 2063
`
`EX. 2064
`
`EX. 2065
`EX. 2066
`
`EX. 2067
`EX. 2068
`
`EX. 2069
`
`EX. 2070
`
`EX. 2071
`
`EX. 2072
`EX. 2073
`EX. 2074
`EX. 2075
`
`EX. 2076
`
`vi
`
`
`
`
`
`I.
`
`INTRODUCTION
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`The Board should deny Petitioner’s request for additional discovery because
`
`the Petitioner has failed to satisfy the Garmin factors. At best, Petitioner is
`
`speculating that something useful regarding its contentions might be uncovered.
`
`Notably absent from the motion is any articulation of what useful information the
`
`production is expected to uncover. Instead, the motion only argues that the
`
`discovery is necessary to allow a “complete evaluation,” whatever that means.
`
`Petitioner’s motion appears to be a prelude for new arguments that are
`
`inconsistent with the petitions and declarations upon which review was instituted.
`
`The petitions relied upon the Sall (Ex. 1007) and Stevenson (Ex. 1015), peer-
`
`reviewed publications that describe the efficacy data of Allergan’s Phase II and
`
`Phase III studies, and stated that these publications contain the necessary
`
`information to answer the question of whether the efficacy results are significant.
`
`Allergan and its declarants (Drs. Sheppard and Loftsson) showed—contrary to
`
`Petitioner’s arguments—that the tear production efficacy data reported in Sall
`
`supported the unexpected results and criticality of the claimed formulation.
`
`Because Sall and Stevenson contradict, rather than support its position, Petitioner
`
`now asks for additional discovery presumably to undercut Sall and Stevenson.
`
`This is a new argument, and prohibited by the Board’s rules.
`
`1
`
`
`
`
`
`Moreover, this is not minor, targeted discovery for particular identified
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`documents. Given the statutory time limits and necessarily streamlined IPR
`
`process (as compared to district court litigation), the Board must be conservative in
`
`ordering additional discovery. See 154 Cong. Rec. S9988-89 (daily ed. Sept. 27,
`
`2008). This request deals with complex and voluminous Phase II and Phase III
`
`clinical trials, which were submitted to FDA for approval of RESTASIS®. The
`
`requested discovery would involve the production of more than 60,000 pages of
`
`documents. The request is not tailored to meet a real need and should be denied.
`
`II. BACKGROUND
`
`
`
`During prosecution, Allergan submitted the declarations of Drs. Schiffman
`
`and Attar. The Examiner stated that the declarations showed the claimed
`
`formulation “is surprisingly critical for the therapeutic effectiveness in the
`
`treatment of dry eye or keratoconjunctivitis sicca” and “provide clear and
`
`convincing objective evidence that establishes the claimed formulations, including
`
`0.05% by weight cyclosporine A and 1.25% by weight castor oil, demonstrate
`
`surprising and unexpected results.” Ex. 1004, pp. 276-77. Petitioner
`
`acknowledges that “much of the same data relied upon as demonstrating
`
`unexpected equivalent efficacy of the 0.05% CsA emulsion and the 0.10% CsA
`
`emulsion [in the declarations] appear identical to graphs published more than one
`
`2
`
`
`
`
`
`year before the alleged priority date” in Sall. Petition at 48 (all citations to
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`IPR2016-01127).
`
`
`
`Petitioner argued the declarations do not demonstrate unexpected results
`
`because they “failed to provide the necessary parameters for scientific
`
`interpretation, including raw data values and error rates.” Petition at 47-48. In
`
`contrast, Petitioner’s expert Dr. Amiji stated that Sall includes the necessary
`
`information “and can therefore answer the question of whether the results reported
`
`therein are significant.” Amiji at ¶ 131. Petitioner then argues that Sall and
`
`Stevenson do not support a conclusion of unexpected results. Petition at 50-51.
`
`
`
`The declarations also refer to PK studies conducted by Allergan.2 These
`
`studies show that less CsA reaches the relevant tissue for tear production—the
`
`lacrimal gland, conjunctiva, and cornea—with the 0.05% emulsion in comparison
`
`to the 0.10% emulsion. Ex. 1004, pp. 190-242. Petitioner and Dr. Amiji, do not
`
`
`2 Allergan previously produced the PK study comparing the two formulations in
`
`the Phase III study, which are also the formulations described in the specifications
`
`of the patents at issue in these IPRs, as Ex. 2026, because its experts relied on the
`
`study. Allergan has now produced the second PK study referenced in the
`
`declarations, which relates to the formulations in the Phase II trials.
`
`3
`
`
`
`
`
`argue these results are inaccurate but, rather, that because the declarations report
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`“no raw values for CsA measured in the eye tissue, it entirely possible that all
`
`emulsions satisfy the concentration threshold for therapeutic efficacy, and that any
`
`increased delivery is immaterial.” See, e.g, Petition at 54; Amiji at ¶ 145.
`
`Petitioner’s argument goes to the conclusion drawn rather than the data itself.
`
`III. LEGAL STANDARD
`
`The Board applies an “interest of justice” standard when deciding whether to
`
`grant additional discovery. 35 U.S.C. §316(a)(5). As outlined in the Garmin case,
`
`the Board typically weigh five factors when considering additional discovery. The
`
`first Garmin factor, most important here, is “more than a possibility and mere
`
`allegation:”
`
`The mere possibility of finding something useful, and mere allegation
`that something useful will be found are insufficient. Thus, the party
`requesting discovery already should be in possession of a threshold
`amount of evidence or reasoning tending to show beyond speculation that
`something useful will be uncovered. “Useful” does not mean merely
`“relevant” or “admissible,” but rather means favorable in substantive
`value to a contention of the party moving for discovery.
`AIA Blog, September 30, 2014, Message from Administrative Patent Judges
`
`Jacqueline Bonilla and Sheridan Snedden: Routine and Additional Discovery in
`
`AIA Trial Proceedings: What is the Difference?
`
`4
`
`
`
`
`
`IV. ARGUMENT
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`A. The Requested Discovery Will Not Uncover Anything Useful
`Petitioner has failed to articulate anything “more than a possibility and mere
`
`allegation” that the requested additional discovery will uncover anything useful.
`
`The petitions do not challenge the results of the conclusion that less CsA makes its
`
`way to the relevant ocular tissues when using the claimed 0.05% emulsion as
`
`compared to the 0.1% emulsion. Nonetheless, Allergan has produced both
`
`pharmacokinetic studies referenced in the declarations. Petitioner requests the
`
`underlying data, but has not shown that the studies are insufficient for its argument.
`
`With respect to the efficacy data, the motion makes only a conclusory
`
`argument. For example, “the absence of the underlying data for the Sall figures
`
`and PK studies precludes a complete evaluation of whether the data support
`
`Allergan’s contentions.” Motion at 6. No specifics of what is to be uncovered is
`
`provided.3 And, as noted above, this argument is inconsistent with arguments
`
`
`3 During the telephone conference with the Board, Petitioner referenced a court
`
`order to wrongly suggest that the court agreed with its position here. Circuit Judge
`
`Bryson, sitting by designation, denied the motion stating: “the fact that Dr.
`
`Schiffman drew his data from the Phase 3 Study and may have obtained several of
`
`his figures from the Sall Article does not necessarily establish that the Sall Article
`
`5
`
`
`
`
`
`made in the petitions, which explicitly argued that Sall includes the necessary
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`information to answer whether the reported results are significant.
`
`This change in tactic is apparently in response to the Patent Owner Response
`
`proving that the claimed emulsion is more effective at increasing tear production
`
`than the prior art formulations. Patent Owner Response at 28-30. The reported
`
`Schirmer results show that the claimed 0.05% emulsion was statically significant
`
`better than placebo at three months while the 0.10% emulsion was not. At all times
`
`the claimed emulsion was numerically superior to the 0.10% emulsion. Based on
`
`thermodynamic principles and the PK data, this result was completely unexpected.
`
`Id. The Board should not allow additional discovery to support the injection of a
`
`new and improper argument into the IPRs.
`
`B. Petitioner’s Reliance On Corning Is Misplaced
`
`In Corning, the petitioner relied upon expert declarations concerning
`
`samples of the prior art compositions prepared for the IPR and tested the samples
`
`for the properties recited in the claims. IPR2013-0043, Paper 27 at 1-2. The
`
`request related to compositions synthesized for the case and explained that the
`
`
`anticipates (or renders obvious) the formulation that is recited in many of the
`
`claims of the patent in suit.” Ex. 2076 at 14.
`
`6
`
`
`
`
`
`declarations were missing information required to confirm that the compositions
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`were those in the alleged prior art and to evaluate the reliability of the tests
`
`performed. Id. On those facts, the Board ordered production of the lab notebooks.
`
`Id. Here, the requested information was not generated by Allergan for this case.
`
`
`
`Even if this request was similar to the request in Corning—which it is not,
`
`because the requested information was not generated by Allergan for this case—
`
`this request is more like the request for samples. But the Board denied that request
`
`because the moving party argued only that samples “are important and useful for
`
`DSM to independently evaluate” and did not explain why cross-examination and
`
`review of documents was insufficient. Id. Here, Petitioner similarly has made
`
`only conclusory arguments that the documents are needed to allow a “complete
`
`evaluation,” does not explain why all of the technical experts in these IPRs—Drs.
`
`Amiji, Sheppard, and Loftsson—were all able to offer opinions without reviewing
`
`the underlying data, and has not explained why it cannot obtain the information it
`
`seeks through cross-examination using the declarations, PK study reports, and the
`
`Phase II and III results reported in Sall and Stevenson.
`
`V. CONCLUSION
`
`For all of these reasons, the Board should deny Petitioner’s motion for
`
`additional discovery.
`
`7
`
`
`
`
`
`
`Date: May 23, 2017
`
`
`
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`
`
`
`
`
`/ Dorothy P. Whelan/
`Dorothy P. Whelan, Reg. No. 33,814
`Fish & Richardson P.C.
`P.O. Box 1022
`Minneapolis, MN 55440-1022
`T: 612-337-2509
`F: 612-288-9696
`
`8
`
`
`
`
`
`
`
`Case No.: IPR2016-01128
`Attorney Docket No.: 13351-0008IP2
`
`
`CERTIFICATE OF SERVICE
`
`Pursuant to 37 CFR §§ 42.6(e)(4) and 42.205(b), the undersigned certifies
`
`that on May 23, 2017, a complete and entire copy of this Patent Owner Allergan,
`
`Inc.’s Opposition to Motion For Discovery was provided via electronic service, to
`
`the Petitioner by serving the correspondence address of record as follows:
`
`
`
`Steven W. Parmelee
`Michael T. Rosato
`Jad A. Mills
`Wilson Sonsini Goodrich & Rosati
`701 Fifth Avenue, Suite 5100
`Seattle, WA 98104-7036
`sparmelee@wsgr.com
`mrosato@wsgr.com
`jmills@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
`
`
`
`
`
`Case No.: 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
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` /Jessica K. Detko/
`
`Jessica K. Detko
`Fish & Richardson P.C.
`60 South Sixth Street, Suite 3200
`Minneapolis, MN 55402
`(612) 337-2516
`
`
`
`
`
`
`
`
`
`
`
`
`