`
`
`
`Paper No. ___
`Filed: October 22, 2018
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioners,
` v.
`BAYER INTELLECTUAL PROPERTY GMBH,
`Patent Owner.
`_____________________________
`
`IPR2018-01143
`Patent No. 9,539,218
`_____________________________
`
`PETITIONER’S PRE-INSTITUTION REPLY
`
`
`
`TABLE OF CONTENTS
`Page
`I.
`BAYER’S CLAIM CONSTRUCTION IS ERRONEOUSLY
`NARROW ....................................................................................................... 1
`II.
`BAYER’S § 325(D) ARGUMENTS ARE UNAVAILING .......................... 3
`III. BAYER’S § 312(A)(3) CASES ARE DISTINGUISHABLE ....................... 4
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`Bayer’s Preliminary Response (Paper 6, “POPR”) asserts a narrow and
`limiting claim construction that is undermined by Bayer’s subsequent conduct.
`Further, the evidence and arguments against the ʼ218 claims are properly set out in
`the Petition and Bayer’s contrary complaints in the POPR should be disregarded.
`BAYER’S CLAIM CONSTRUCTION IS ERRONEOUSLY NARROW
`I.
`Bayer asks the Board to ignore evidence submitted with the Petition about
`the meaning of the term “rapid-release tablet” because the specification allegedly
`“explains and defines” the claim term rapid-release tablet “without ambiguity or
`incompleteness,” such that “there is no need to search further for the meaning of
`the term.” Id. POPR, 5, 14-15. But Bayer’s recent actions in the district court show
`its proposed definition is neither unambiguous nor complete.
`On September 18, 2018, after the district court adopted Bayer’s proposed
`construction verbatim, Bayer asked the district court to further construe Bayer’s
`construction of rapid-release tablet. EX1066. In response, Mylan asked the court to
`hold Bayer to its litigation argument that “there is no need for the Court to search
`further for the meaning of the phrase” other than adopting the “express definition”
`in the specification. EX1067. Bayer’s reply asked the court to consider extrinsic
`evidence. EX1068. On September 28, 2018, the court expressly rejected Bayer’s
`request to “further construe” the “lexicographic definition.” EX1069. Bayer’s
`request for further claim construction in district court contradicts the argument that
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`its “definition” construction in the POPR is unambiguous and complete, and
`confirms that evidence Mylan submitted with its Petition regarding the meaning of
`“rapid-release tablet” should be given substantial weight.
`Bayer’s district court briefing also resolves whether Bayer concedes
`Forsman satisfies the rapid-release limitation of claim 1. In its POPR, Bayer
`argued that Forsman’s “disclosure of a rapid-release tablet according to the
`Board’s prior construction” is merely something that “the Petition alleges.” POPR
`at 2-3. In its district court briefing, Bayer discloses its interpretation of its rapid-
`release construction. EX1066; EX1068. Bayer can no longer equivocate its view
`on how its interpretation applies: Forsman satisfies the rapid-release element.
`Bayer argues in its POPR (6-9) that the Board should adopt claim
`constructions from other proceedings. But the district court was not applying the
`broadest reasonable construction. And the fact finding in the ex parte appeal (FF4)
`was based on a limited record. The ’218 patent specification does not say that
`rapid-release tablets are limited to only those tablets with a certain Q value. The
`POPR (13) argues the specification expressly identifies preferred embodiments as
`such immediately before and after the Q value description. But defined terms are
`expressly identified by quote marks and are each called a “term;” “rapid-release
`tablet” is not. If Bayer desires to limit the claims as it now proposes, Congress has
`provided a mechanism for this: a post-institution motion to amend.
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`Bayer concedes that the EPO Proceedings involved “the counterpart of the
`’218 patent,” but argues that its embrace of a broader construction before the EPO
`is irrelevant. POPR, 14-16. But the EPO’s adoption of that construction confirms
`Mylan’s construction here is reasonable. Pet., 25-26.
`II. BAYER’S § 325(D) ARGUMENTS ARE UNAVAILING
`Bayer argues that Ground 1 should be denied if the Board adopts Bayer’s
`narrowing claim construction. For the reasons discussed above in Section I, the
`Board should adopt Mylan’s claim construction and institute Ground 1.
`Regarding Ground 2, Bayer argues (POPR at 3, 24) that Forsman is
`cumulative to prior art considered during prosecution because the specification
`generically references a publication for measuring Q values. But disclosing a test is
`not the same as disclosing a tablet with the requisite Q value and teaching its use
`for thromboembolic disorders. Pet., 3, 10-11, 17-18, 46-48 (discussing EX1007).
`Bayer concedes (POPR, 23) that, following its ex parte appeal, “the
`Examiner did not fill the evidentiary gap identified by the Board.” That gap is
`precisely the one filled by the new evidence and argument submitted with Mylan’s
`Petition. Bayer errs in describing that gap and in arguing that the Petition fails to
`address it with new evidence. The gap was not (contra POPR at 3, 23-24) whether
`“the pharmacokinetics of rivaroxaban” made it amenable to once-daily dosing in
`rapid-release dosage form. Indeed, the ex parte appeal found this would have been
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`obvious in light of Kubitza abstracts #3004 and #3010 and the ’610 publication.
`EX1004, 0114-17. The question on return to the examiner was whether the prior
`art rendered obvious the use of a tablet having a Q value (30 minutes) of 75% in
`place of a rapid-release liquid that achieved maximum plasma concentrations
`within 30 minutes. Id. Art not considered by the Examiner establishes that this
`would have been desirable, obvious, and easy to do. Pet., 3, 10-11, 30-31, 39-40,
`46-48. Unlike the cases Bayer cites, the new art and evidence provided with the
`Petition are not merely cumulative of evidence the Office previously considered.
`III. BAYER’S § 312(A)(3) CASES ARE DISTINGUISHABLE
`Bayer’s argument that the Petition should be denied under § 312(a)(3)
`because EX1006 comprises three abstracts and is treated as a single reference is
`without merit. First, the three abstracts are related to one another and appear within
`the same chapter of a single publication. Bayer asserts that it cannot tell whether all
`three Kubitza abstracts are asserted, but concedes “the Petition relies on each one
`separately for different disclosures.” POPR, 26-27. The Petition asserts all three
`abstracts with specificity and particularity, and explains why a POSA had good
`reason to use these teachings together to select a dosing regimen, as found during
`the ex parte appeal. Pet., 8-10, 32-46; EX1004, 0114-15. The abstracts are indexed
`together by author, Kubitza, and by subject matter. EX1006, 0018-19.
`Bayer asserts (at 29) the Petition (at 47) fails to identify which Kubitza
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`abstract is discussed. The cite to EX1006 at 0015 (abstract #3010) appears in the
`same paragraph, on page 46. The Petition cites this teaching repeatedly. Pet., 10,
`45-46, 46-47. Bayer’s argument (26, 31) that institution should be denied because
`the claim chart cites abstract #3003, which corroborates the disclosure of abstract
`#3010 that maximum inhibition is observed within 2 hours, has no merit.
`Second, the Petition does not assert several unrelated references in the
`alternative without proposing “any specific combination” that satisfies the claim
`limitations. See Dynamic Drinkware, IPR2013-00131, Paper 16 at 3, 16-17; see
`also TRW, IPR2014-00293, Paper 21 at 3-4; Gea, IPR2014-00054, Paper 11 at 17-
`18, (17 unrelated references, redundant to instituted ground); Hopkins, IPR2015-
`00609, Paper 9 at 12-13 (multiple grounds argued together failed to identify which
`references apply to this ground and how, and failed to address a claim limitation).
`Third, the Petition did not physically combine separate documents published
`in different places at different times into a single exhibit. See, e.g., Google, CBM
`2016-00021, Paper 11 at 42-43; Enovate, IPR2015-00300, Paper 12 at 3. That
`would violate Board rules. 37 C.F.R. § 42.6(a)(3). In Ford, IPR2015-00800, Paper
`12, the petition referred to six publications from various years as though one
`publication. Id. at 12. The Board found this permissible for five of them. Id. at 13-
`15. As discussed above, the Petition sets forth the grounds and motivation to
`combine with particularity. Mylan requests institution.
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` Dated: October 22, 2018
`
`
`
`
`Respectfully submitted,
`/ Steven W. Parmelee /
`Steven W. Parmelee, Lead Counsel
`Reg. No. 31,990
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`
`
`IV. APPENDIX – LIST OF EXHIBITS
`Description
`Exhibit No.
`U.S. Patent No. 9,539,218 to Misselwitz et al.
`1001
`Declaration of Dr. Leslie Z. Benet, Ph.D.
`1002
`Declaration of Dr. Neil E. Doherty, M.D.
`1003
`Prosecution History of the 9,539,218 patent to Misselwitz et al.
`1004
`U.S. Patent Publication No. 2003/0153610 to Straub et al.
`1005
`Kubitza Abstracts #3003, #3004, #3010, 45th Annual Conference of
`the American Society of Hematology, 102 BLOOD (2003), 807a-
`1006
`815a
`International Patent Publication No. WO 2000/013671 to Forsman
`1007
`et al.
`U.S. Patent No. 7,157,456
`1008
`U.S. Patent No. 7,592,339
`1009
`Morales, T., Preventing Economy Class Syndrome, CBS News,
`September 13, 2004; accessed from
`1010
`https://www.cbsnews.com/news/preventing-economy-class-
`syndrome/ on May 23, 2018
`Isayev et al., “Economy Class” Stroke Syndrome?, 58 NEUROLOGY
`1011
`(2002) 960-61
`Foerch et al., Economy Class Stroke Syndrome, Correspondence, 59
`1012
`NEUROLOGY (2002) 962-63
`Guidance for Industry, Bioavailability and Bioequivalence Studies
`for Orally Administered Drug Products – General
`Considerations, U.S. Department of Health and Human Services,
`1013
`Food and Drug Administration, Center for Drug Evaluation and
`Research (CDER), 2002
`- 7 -
`
`
`
`1014
`1015
`1016
`1017
`1018
`1019
`1020
`1021
`1022
`1023
`1024
`1025
`
`Aulton et al., Chapter 27 Tablets and Compaction;
`PHARMACEUTICS: THE SCIENCE OF DOSAGE FORM DESIGN, 2nd
`Edition (2002) Churchill Livingston (Elsevier Ltd.), 397-441
`European Patent Office Opposition Proceeding re EP 1 845 961,
`Patentee’s Response to the Notice of Oppositions
`European Patent Office Revocation Decision re EP 1 845 961 (April
`30, 2018)
`Carville et al., Thrombus precursor protein (TpPTM): marker of
`thrombosis early in the pathogenesis of myocardial infarction, 42
`CLIN. CHEM. (1996) 1537-41
`Leadley et al., Coagulation Factor Xa Inhibition: Biological
`Background and Rationale, 1 CURR. TOP. MED. CHEM. (2001)
`151-59
`Goldhaber, Pulmonary embolism, 363 LANCET (2004) 1295-1305
`Perzborn et al., In vitro and in vivo studies of the novel
`antithrombotic agent BAY 59-7939 – an oral, direct Factor Xa
`inhibitor, 3 J. THROMB. HAEMOST. (2005) 514-21
`18th International Congress on Thrombosis Abstracts; 33
`PATHOPHYSIOL. HAEMOST. THROMB. (2003) Suppl. 2 Excerpt
`Goodman and Gilman’s The Pharmacological Basis of Therapeutics
`(1985), 7th Edition, McGraw-Hill Medical Publishing Division
`Birkett et al., Pharmacokinetics made easy 11 Designing dose
`regimens, 19 AUST. PRESCR. (1996) 76-78
`Iskedjian et al., Relationship Between Daily Dose Frequency and
`Adherence to Antihypertensive Pharmacotherapy: Evidence from
`a Meta-Analysis, 24 CLIN. THER. (2002) 302-16
`Lovenox Injection (Aventis) 11/27/2000 Supplemental Approval
`[New Indication], S36 Approval Letter; Approvable Letter; Final
`Labeling – FOI Document #5243106A (2000)
`- 8 -
`
`
`
`1026
`1027
`1028
`1029
`1030
`1031
`1032
`1033
`1034
`1035
`1036
`
`Al-Yaseen et al., The safety of dosing dalteparin based on actual
`body weight for the treatment of acute venous thromboembolism
`in obese patients, 3 J. THROMB. HAEMOST. (2005) 100-02
`Fragmin (Pharmacia and Upjohn) 03/30/1999 Supplemental
`Approval [Prophylaxis of Deep Vein Thrombosis]: S8 Approval
`Letter; Final Labeling – FOI Document #5243139A (1999)
`Yeager et al., Low-Molecular-Weight Heparin in Outpatient
`Treatment of DVT, 15 AM. FAM. PHYSICIAN (1999) 945-52
`Nutescu et al., Direct Thrombin Inhibitors for Anticoagulation, 38
`ANN. PHARMACOTHER. (2004) 99-109
`Lieberman et al., Pharmaceutical Dosage Forms: Tablets, Volume
`1, Second Edition (1989), Marcel Decker, Inc.
`Roehrig et al., Discovery of the novel antithrombotic agent BAY 59-
`7939, an orally active, direct factor Xa inhibitor, 228th ACS
`NATIONAL MEETING, 2004
`International Patent Publication No. WO 2003/101423 to
`Abrahmsén et al.
`Saccone et al., Statistical Properties of the Dissolution Test of USP,
`11 DISSOLUTION TECH. (2004) 25-28
`Wright et al., Clinical Pharmacokinetics of Alprazolam Extended
`Release: A Summary, 56 CUR. THER. RES. (1995) 947-56
`Camerlingo et al., Immediate Anticoagulation with Heparin for
`First-Ever Ischemic Stroke in the Carotid Artery Territories
`Observed Within 5 Hours of Onset, 51 ARCH. NEUROL. (1994)
`462-67
`Golub et al. Physiologic considerations in drug absorption from the
`gastrointestinal tract, 78 J. ALLERGY CLIN. IMMUNOL. (1986)
`689-94
`- 9 -
`
`
`
`1037
`1038
`1039
`1040
`1041
`1042
`1043
`1044
`1045
`1046
`1047
`1048
`1049
`
`Bueller et al., Antithrombotic Therapy for Venous Thromboembolic
`Disease, The Seventh ACCP Conference on Antithrombotic and
`Thrombolytic Therapy, 126 CHEST (2004) 401S-428S
`Martineau et al., Low-Molecular-Weight Heparins in the Treatment
`of Deep-Vein Thromboembolism, 32 ANN. PHARMACOTHER.
`(1998) 588-98
`Ageno et al., Low-molecular-weight heparins in the treatment
`venous thromboembolism, 1 CURR. CONTROL TRIAL CARDIOVASC.
`MED. (2000) 102-06
`CLINICAL PHARMACOKINETICS, CONCEPTS AND APPLICATIONS, Lea
`and Febiger, 3rd Edition (1995), 83-105
`Eriksson et al., A Once-Daily, Oral, Direct Factor Xa Inhibitor,
`Rivaroxaban (BAY 59-7939), for Thromboprophylaxis After Total
`Hip Replacement, 114 CIRCULATION (2006) 2374-81
`Weinz et al., In vitro metabolism of BAY 59-7939—An oral, direct
`factor Xa inhibitor, 7th INTERNATIONAL ISSX MEETING, 2004,
`DRUG METAB. REV. 36 Suppl. 1 (2004) 98
`Weitz et al., New Anticoagulants for Treatment of Venous
`Thromboembolism, 110 CIRCULATION (2004) I-19-I-26
`European Patent No. 1 845 961 to Misselwitz et al.
`Mann et al., What is all that thrombin for?, 1 J. THROMB. HAEMOST.
`(2003) 1504-14
`Curriculum Vitae of Leslie Z. Benet, Ph.D.
`Benet et al., Changes in plasma protein binding have little clinical
`relevance, 71 CLIN. PHARMACOL. THER. (2002) 115-21
`Kaiser, Factor Xa – a promising target for drug development, 59
`CELL. MOL. LIFE SCI. (2002) 189-92
`Moonis et al., Considering the Role of Heparin and Low Molecular
`Weight Heparins in Acute Ischemic Stroke, 33 STROKE (2002)
`1927-33
`- 10 -
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`
`
`1050
`1051
`1052
`1053
`1054
`1055
`1056
`1057
`1058
`1059
`1060
`1061
`1062
`1063
`1064
`1065
`1066
`
`Rudnic et al., Chapter 45: Oral Solid Dosage Forms, REMINGTON’S
`21ST EDITION: THE SCIENCE AND PRACTICE OF PHARMACY (D.
`Troy ed., 2005)
`Lowe, Venous and arterial thrombosis: epidemiology and risk
`factors at various ages, 47 MATURITAS (2004) 259-63
`Curriculum Vitae of Neil E. Doherty, M.D.
`Complaint; Bayer Intellectual Property GMBH et al. v. Mylan
`Pharmaceuticals Inc., No. 1:17-cv-00584
`Chapter 711 Dissolution, THE UNITED STATES PHARMACOPEIA
`(USP) 2000
`Bauer et al., Fondaparinux, a Synthetic Pentasaccharide: The First
`in a New Class of Antithrombotic Agents – The Selective Factor
`Xa Inhibitors, CARDIOVASC. DRUG REV. 20(1): 37-52 (2002)
`Coumadin® Label (1999)
`Refludan® Label (2004)
`Angiomax® Label (2000)
`Acova® Label (2000)
`Pradaxa® Label (2015)
`Xarelto® Label (2012)
`Eliquis® Label (2014)
`Savaysa® Label (2015)
`Bevyxxa® Label (2017)
`May 24, 2017 Email from Alexander Zolan to Ellie Steiner
`PROTECTIVE ORDER MATERIAL: September 18, 2018 Bayer
`Intellectual Property GmBH Letter to Judge Richard G. Andrews
`- 11 -
`
`
`
`1066
`1067
`1067
`1068
`1068
`1069
`1070
`1071
`
`September 18, 2018 Bayer Intellectual Property GmBH Letter to
`Judge Richard G. Andrews
`PROTECTIVE ORDER MATERIAL: September 21, 2018 Mylan
`Pharmaceuticals Inc. Letter to Judge Richard G. Andrews
`September 21, 2018 Mylan Pharmaceuticals Inc. Letter to Judge
`Richard G. Andrews
`PROTECTIVE ORDER MATERIAL: September 24, 2018 Bayer
`Intellectual Property GmBH Letter to Judge Richard G. Andrews
`September 24, 2018 Bayer Intellectual Property GmBH Letter to
`Judge Richard G. Andrews
`Order; Bayer Intellectual Property GMBH et al. v. Taro
`Pharmaceutical Industries, LTD., et al., No. 1:17-cv-00462
`Protective Order
`Protective Order Redline
`
`
`- 12 -
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`CERTIFICATE OF SERVICE
`
`This is to certify that I caused to be served true and correct copies of the
`foregoing Petitioners’ Pre-Institution Reply and corresponding exhibits 1066
`through 1071 on this 22nd day of October, 2018, on the Patent Owner at the
`correspondence address of the Patent Owner as follows:
`Dov P. Grossman
`Ben Picozzi
`WILLIAMS & CONNOLY LLP
`725 Twelfth St. NW
`Washington, DC 20005
`Email: dgrossman@wc.com
`Email: bpicozzi@wc.com
`
`
`
`
`/ Steven W. Parmelee /
`Dated: October 22, 2018
`
` Steven W. Parmelee,
`
`
` Reg. No. 31,990
`
`
`
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