Filed on behalf of: Mylan Pharmaceuticals Inc.
`By: Steven W. Parmelee
`
`Michael T. Rosato
`Jad A. Mills
`Wilson Sonsini Goodrich & Rosati
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________________
`
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`BAYER INTELLECTUAL PROPERTY GMBH,
`Patent Owner.
`
`_____________________________
`
`Case No. IPR2018-01143
`Patent No. 9,539,218
`_____________________________
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 9,539,218
`
`
`
`
`
`
`
`
`By: Steven W. Parmelee
`
`Michael T. Rosato
`Jad A. Mills
`Wilson Sonsini Goodrich & Rosati
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________________
`
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`BAYER INTELLECTUAL PROPERTY GMBH,
`Patent Owner.
`
`_____________________________
`
`Case No. IPR2018-01143
`Patent No. 9,539,218
`_____________________________
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 9,539,218
`
`
`
`
`
`
`
`
`
`I.
`
`TABLE OF CONTENTS
`
`INTRODUCTION .............................................................................................. 1
`A.
`Brief Overview of the ’218 Patent....................................................... 3
`B.
`Brief Overview of the Prosecution History ......................................... 4
`C.
`Brief Overview of the Scope and Content of the Prior Art .................. 6
`D.
`Brief Overview of the Level of Skill in the Art ................................. 11
`II.
`GROUNDS FOR STANDING ............................................................................. 13
`III. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8 ........................................... 13
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED ......................................... 15
`V.
`CLAIM CONSTRUCTION ................................................................................ 15
`VI. BACKGROUND KNOWLEDGE IN THE ART PRIOR TO JANUARY 31, 2005 .......... 26
`VII. DETAILED EXPLANATION OF GROUNDS FOR UNPATENTABILITY .................... 31
`A.
`the ’610 Publication and Kubitza Abstracts....................................... 31
`B.
`the ’610 Publication, Kubitza Abstracts, and Forsman. ..................... 46
`VIII. NO UNEXPECED RESULTS ............................................................................ 50
`IX. CONCLUSION ............................................................................................... 55
`CERTIFICATE OF COMPLIANCE ...................................................................... 56
`X.
`XI. PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15(A) AND 42.103 ...................... 57
`XII. APPENDIX – LIST OF EXHIBITS...................................................................... 58
`
`[Ground 1] Claims 1-4 are Obvious under 35 U.S.C. § 103 over
`
`[Ground 2] Claims 1-4 are Obvious under 35 U.S.C. § 103 over
`
`
`
`i
`
`
`
`I.
`
`INTRODUCTION
`
`Mylan Pharmaceuticals Inc. (“Petitioner”) requests inter partes review of
`
`U.S. Patent No. 9,539,218 to Misselwitz et al. (“the ’218 patent,” EX1001), which
`
`issued on January 10, 2017. Unites States Patent and Trademark Office (USPTO)
`
`records indicate the ’218 patent is assigned to Bayer Intellectual Property GmbH
`
`(“Patent Owner”). This Petition demonstrates that there is a reasonable likelihood
`
`that claims 1-4 of the ’218 patent are unpatentable over prior art.
`
`The ʼ218 patent is directed to administering an anticoagulant, the known
`
`factor Xa (“FXa”) inhibitor rivaroxaban, to a patient in need of treating any one of
`
`the thromboembolic disorders pulmonary embolism (PE), deep vein thrombosis
`
`(DVT), or stroke. The method of the ʼ218 patent is practiced by administering
`
`rivaroxaban no more than once daily for at least five consecutive days in a rapid-
`
`release tablet to a patient in need. On appeal from the Examiner’s rejection during
`
`prosecution of the ’218 patent, the Board evaluated claims that were identical to
`
`the issued claims except that they recited “a rapid release oral dosage form” instead
`
`of “a rapid-release tablet.” The Board affirmed that the claims were obvious
`
`because prior art describing the phase 1 human clinical trials of rivaroxaban
`
`disclosed once daily dosing of rivaroxaban for at least five consecutive days and
`
`disclosed rivaroxaban administration in a liquid rapid-release oral dosage form. As
`
`for a dependent claim direct to a rapid-release tablet, the Board found that the
`
`
`
`1
`
`
`
`evidence of record did not allow them to conclude the tablets of rivaroxaban
`
`described in the prior art were “rapid-release.” Subsequently, an Examiner’s
`
`Amendment narrowed the claimed rapid-release oral dosage form to a rapid-
`
`release tablet and allowed the claims. In other words, the ’218 patent issued based
`
`on the alleged innovation of tablet administration.
`
`The claims of the ʼ218 are unpatentable as obvious. As explained in Ground
`
`1, U.S. Patent Publication No. 2003/0153610 (“the ’610 publication”) teaches
`
`administration of rivaroxaban and related FXa inhibitors for the prevention and
`
`therapy of thromboembolic disorders, including pulmonary embolisms (PE), deep
`
`vein thromboses (DVT), and stroke. Naturally, the ’610 publication teaches that
`
`the active compounds may be converted in a known manner into customary
`
`formulations, including tablets. Kubitza Abstracts disclose rivaroxaban’s
`
`advancement into human clinical trials for the prevention and therapy of
`
`thromboembolic disorders. Consistent with prior art anticoagulants administered
`
`for the prevention and therapy of thromboembolic disorders, Kubitza Abstracts
`
`describe administering rivaroxaban to humans once-daily or twice-daily for at least
`
`five consecutive days. Kubitza Abstracts also disclose administration of
`
`rivaroxaban in rapid-release oral dosage forms, including in solution and in tablet
`
`forms. Kubitza Abstracts also disclose pharmacological and pharmacokinetic data
`
`
`
`2
`
`
`
`supporting the feasibility of once-daily administration of rivaroxaban in a rapid-
`
`release tablet for the prevention and therapy of thromboembolic disorders.
`
`As explained in Ground 2, the claims of the ’218 patent are obvious even if
`
`the claims were narrowed to a particular embodiment of a rapid-release tablet
`
`having a Q value (30 minutes) of 75%, in view of the ʼ610 publication, Kubitza
`
`Abstracts, and Forsman. Forsman discloses a rapid-release tablet having a Q value
`
`(30 minutes) of at least 75% and administration of an oral anticoagulant in a rapid-
`
`release oral tablet for the prophylaxis and/or therapy of thromboembolic disorders.
`
`Petitioners thus request that Inter Partes review be instituted and claims 1-4
`
`of the ’218 patent be cancelled as unpatentable under 35 U.S.C. § 103.
`
`A. Brief Overview of the ’218 Patent
`
`The ’218 patent is entitled “Prevention and Treatment of Thromboembolic
`
`Disorders.” It has four claims. Claim 1 of the ’218 patent recites:
`
`A method of treating a thromboembolic disorder comprising
`
`administering a direct factor Xa inhibitor that is 5-Chloro-N-({(5S)-2-
`
`oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl} methyl)-
`
`2-thiophenecarboxamide no more than once daily for at least five
`
`consecutive days in a rapid-release tablet to a patient in need thereof,
`
`wherein the thromboembolic disorder is selected from the group
`
`consisting of pulmonary embolisms, deep vein thromboses, and
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`stroke.
`
`
`
`3
`
`
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`EX1001, 10:63-11:5; EX1002, ¶¶14-17; EX1003, ¶¶8-9; see also EX1002, ¶¶19-
`
`22.
`
`Claims 2-4 of the ’218 patent depend from claim 1 and recite:
`
`Claim 2: The method of claim 1, wherein the thromboembolic
`
`disorder is pulmonary embolisms.
`
`Claim 3: The method of claim 1, wherein the thromboembolic
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`disorder is deep vein thrombosis.
`
`Claim 4: The method of claim 1, wherein the thromboembolic
`
`disorder is stroke.
`
`EX1001, 11:6-11; EX1002, ¶18; EX1003, ¶10.
`
`B.
`
`Brief Overview of the Prosecution History
`
`U.S. Patent Application No. 11/883,218 (“the ’218 application”) was filed
`
`on July 16, 2008 as a national stage entry of PCT EP2006/000431, filed on January
`
`19, 2006, and claims priority to European Application No. EP 05001893, filed on
`
`January 31, 2005. EX1002, ¶14; EX1003, ¶11.
`
`Following a restriction requirement, the Examiner rejected the claims based
`
`on any of the commonly assigned U.S. Patent No. 7,157,456 (EX1008), U.S.
`
`Patent No. 7,592,339 (EX1009), or the ’610 publication (EX1005), in light of two
`
`abstracts by Kubitza et al. found in a single abstract book: Kubitza et al. Abstract
`
`#3004 (during prosecution referred to as “Kubitza 1”), #3010 (during prosecution
`
`referred to as “Kubitza 2”), 102 BLOOD (2003) 811a, 813a. EX1004 at 0255-70;
`
`
`
`4
`
`
`
`EX1002, ¶¶23-26; see also EX1006 (“Kubitza Abstracts”) at 0013 (Abstract
`
`#3004), 0015 (Abstract #3010).
`
`After final rejection, Applicants appealed to the Board. EX1004 at 0154-68,
`
`0173-78; EX1002, ¶27; see also EX1004 at 0211-13, 0235-37. The Board’s June 3,
`
`2016 decision (Appeal 2014-004087) affirmed the Examiner with respect to rapid-
`
`release oral dosage forms administered once-daily for at least five consecutive days
`
`but reversed the Examiner with respect to a rapid-release tablet. EX1004 at 0109-
`
`17; EX1002, ¶¶27-33.
`
`The prosecution history does indicate the Examiner performed a new search
`
`for art regarding rapid-release tablets following remand from the Board. EX1002,
`
`¶34. A Notice of Allowance issued accompanied by an examiner’s amendment
`
`changing “rapid-release oral dosage form” to “rapid-release tablet.” EX1004 at
`
`0054-55. The Reasons for Allowance stated that the cited art did not disclose “the
`
`instantly claimed method wherein a rapid-release tablet is utilized,” as opposed to a
`
`rapid-release liquid dosage form that had been determined to be obvious by the
`
`Board. Id. The Examiner reaffirmed that the cited prior art references “render
`
`obvious a method of treating the claimed thromboembolic disorders comprising
`
`administering riv[a]roxaban no more than only [once] daily for at least five
`
`consecutive days in a rapid release oral dosage form…,” and this statement was not
`
`
`
`5
`
`
`
`subsequently challenged by Applicants. Id. The ’218 application issued on January
`
`10, 2017 as the ’218 patent.
`
`C. Brief Overview of the Scope and Content of the Prior Art
`
`In obviousness cases, Graham v. John Deere Co. of Kansas City requires an
`
`evaluation of any differences between the claimed subject matter and the asserted
`
`prior art. 383 U.S. 1, 17-18 (1966). As noted in KSR Int’l Co. v. Teleflex Inc., the
`
`obviousness inquiry may account for inferences that would be employed by a
`
`person of ordinary skill in the art. 550 U.S. 398, 418 (2007); EX1002, ¶90.
`
`1) The ’610 Publication (EX1005)
`
`The ’610 publication, which published on August 14, 2003, and is available
`
`as prior art to the claims of the ’218 patent under 35 U.S.C. § 102(b). The abstract
`
`of the ’610 publication states: “The invention relates to the field of blood
`
`coagulation. Novel oxazolidinone derivatives of the general formula (I)[,]
`
`processes for their preparation and their use as medicinally active compounds for
`
`the prophylaxis and/or treatment disorders are described.” EX1005, Abstract;
`
`EX1002, ¶¶91-92; EX1003, ¶¶73-74. The ’610 publication expressly discloses the
`
`synthesis, chemical name, and molecular structure of 5-chloro-N-({(5S)-2-oxo-3-
`
`[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-
`
`thiophenecarboxamide (rivaroxaban) as part of a class of oxazolidinone
`
`compounds it teaches are useful for the prophylaxis and/or therapy of
`
`
`
`6
`
`
`
`thromboembolic disorders EX1005, ¶¶1, 3, 355-36, 617-35 (Example 44); see also
`
`id. at claims 10-11, 14. The ’610 publication specifically claims rivaroxaban and
`
`teaches a “[v]ery particular preference” for it. EX1005, ¶145; see also id. at claim
`
`7.
`
`The ’610 publication teaches that these compounds “act in particular as
`
`anticoagulants and can therefore preferably be employed in medicaments for the
`
`prophylaxis and/or therapy of thromboembolic disorders,” particularly including,
`
`stroke, pulmonary embolism, and deep venous thrombosis, among others. EX1005,
`
`¶356. The ’610 publication discloses that these compounds “act in particular as
`
`selective inhibitors of the blood coagulation factor Xa,” and that they cause “an
`
`unexpected, strong and selective inhibition of factor Xa[.]” EX1005, ¶¶359-60,
`
`362. The ’610 publication discloses that rivaroxaban has an IC50 for inhibiting
`
`factor Xa of 0.7 nM, one of only three sub-nanomolar factor Xa IC50’s disclosed
`
`therein. EX1005, ¶635; EX1003, ¶73. The ’610 publication thus discloses “a
`
`method of the prophylaxis and/or treatment of disorders of the human or animal
`
`body, in particular the abovementioned disorders, using compounds of the general
`
`formula (I),” which includes rivaroxaban. EX1005, ¶364; see also id. at claims 7,
`
`10-11, 14; EX1002, ¶92.
`
`The ’610 publication teaches that these compounds “are distinguished” from
`
`conventional preparations for treating thromboembolic disorders:
`
`
`
`7
`
`
`
`…in particular by the fact that a greater therapeutic range is achieved
`
`by selective inhibition of factor Xa. For a patient, this means a lower
`
`risk of, bleeding …. Moreover—owing to the mechanism—the onset
`
`of action is more rapid. Above all, however, the compounds according
`
`to the invention permit an oral administration form, which is a further
`
`advantage of the therapy with the compounds….
`
`EX1005, ¶373; EX1002, ¶92.
`
`The ’610 publication states “[a]ll customary administration forms are
`
`suitable for administration of the compounds according to the invention,” that
`
`“[v]ery particular preference is given to oral administration, this being a further
`
`advantage with respect to the prior art therapy of thromboembolic disorders,” and
`
`that the active “can be converted in a known manner into the customary
`
`formulations, such as tablets[.]” EX1005, ¶¶366-67; EX1002, ¶93. The ’610
`
`publication also teaches that “it has proven advantageous in the case of oral
`
`administration to administer amounts of these compounds from approximately 0.01
`
`to 50 mg/kg, preferably approximately 0.1 to 10 mg/kg, in particular
`
`approximately 0.5 to 8 mg/kg, of body weight to achieve effective results.” Id. at
`
`¶371; EX1002, ¶94; EX1003, ¶¶78-79.
`
`2) Kubitza Abstracts (EX1006)
`
`Kubitza Abstracts were published in 2003 and are available as prior art to
`
`the claims of the ’218 patent under 35 U.S.C. § 102(b). EX1003, ¶75. Kubitza
`
`
`
`8
`
`
`
`Abstracts teach that rivaroxaban “is an innovative, oral, direct Factor Xa inhibitor
`
`in development for the prevention and treatment of thromboembolic diseases.”
`
`EX1006 at 0013, 0015; EX1002,¶¶96-97; EX1003, ¶77. They also teach that FXa
`
`inhibitors “exert their antithrombotic effects through inhibition of thrombin
`
`generation.” E.g., EX1006 at 0013 (Abstract #3003). Each of the Kubitza Abstracts
`
`reports phase I clinical trial results assessing the safety and antithrombotic effects
`
`of orally administered rivaroxaban in human subjects.
`
`Abstract #3003 reports the effect of rivaroxaban on thrombin generation
`
`after human subjects received a single 5 mg or 30 mg dose. EX1006 at 0013;
`
`EX1002, ¶97. Abstract #3003 in fact confirms that “[a] single 30 mg dose [of
`
`rivaroxaban] exerted a sustained effect in some assays of thrombin generation for
`
`up to 24 hours.” EX1006 at 0013; EX1002, ¶97; EX1003, ¶77.
`
`Abstract #3004 reports that rivaroxaban exhibits “predictable dose-
`
`dependent pharmacodynamics and pharmacokinetics without signs or symptoms of
`
`bleeding” after human subjects received oral doses of rivaroxaban of “5 mg od,
`
`bid, or tid, or 10 mg, 20 mg, or 30 mg bid for 5 days with food.” EX1006 at 0013;
`
`EX1002, ¶98. Abstract #3004 also reports that “[t]here were no differences
`
`between the PD effects on day 1 versus day 7 at any dose step” and that “[r]elevant
`
`changes in the PD parameters were still present [for all doses] after 12 hours.”
`
`EX1006 at 0013. Abstract #3004 also reports that rivaroxaban “did not affect
`
`
`
`9
`
`
`
`bleeding time at any dose step,” that maximum plasma concentrations were
`
`“reached after 2.5-4 hours,” and that “the terminal half life was 4-6 hours.”
`
`EX1006 at 0013. Importantly, it is reported that orally administered rivaroxaban
`
`“was safe and well tolerated in doses up to 30 mg bid.” Id.; EX1002, ¶98.
`
` Abstract #3010 reports pharmacodynamic and pharmacokinetic data of
`
`rivaroxaban after human subjects received either a single tablet dose of “1.25 to 80
`
`mg…or a 5 or 10 mg dose as oral solution.” EX1006 at 0015; EX1002, ¶99.
`
`Rivaroxaban “showed a rapid onset of action with maximal effects being observed
`
`after 2 hours.” EX1006 at 0015. Abstract #3010 teaches that the oral solution
`
`achieved “maximal plasma concentrations…after 0.5 hours…leading to a terminal
`
`half-life of 3-4 hours.” EX1006 at 0015. The tablet showed “[l]ower peak
`
`concentrations of approximately 50%...2 hours after administration of the tablet.”
`
`Both dosage forms, however, “were comparable in terms of AUC [(area under the
`
`curve)].” EX1006 at 0015. Abstract #3010 confirms that rivaroxaban is “safe and
`
`well tolerated across a wide range of oral doses (1.25-80 mg)[.]” Id.; EX1002, ¶99.
`
`3) Forsman (EX1007)
`
`Forsman was published as International Publication No. WO 2000/013671
`
`on March 16, 2000 (“Forsman,” EX1007) and thus is available as prior art to the
`
`claims of the ’218 patent under 35 U.S.C. § 102(b).
`
`
`
`10
`
`
`
`Forsman teaches “low molecular weight thrombin inhibitor[s] formulated as
`
`immediate release (IR) tablets” and the use of this “formulation in the prophylaxis
`
`and / or treatment of thromboembolism.” EX1007, 1:6-9; EX1002, ¶100. Forsman
`
`teaches “immediate release formulation[s] based on conventional manufacturing
`
`processes” that provide a “release [of] 85% or more of stated amount within 30
`
`min.” Id. at 1:18-21, 2:4-5, 3:29-4:2; EX1002, ¶¶100, 104. Forsman demonstrates
`
`that its immediate release tablets release 94% of active ingredient at pH 1 and pH
`
`6.8 within 30 minutes using the USP Apparatus 2. EX1007, 7:1-8:2; see also id. at
`
`FIG. 1; EX1002, ¶¶102-03; EX1003, ¶95.
`
`D. Brief Overview of the Level of Skill in the Art
`
`As of January 2005, a person having ordinary skill in the art would include
`
`an individual or a team of individuals having some combination of the following
`
`skills and experience: (i) experience in pharmacology, pharmacokinetics,
`
`toxicology, and formulation; (ii) an understanding of the role of anticoagulants,
`
`including factor Xa inhibitors, in the treatment and prevention of
`
`thromboembolism disorders; and (iii) the ability to understand work presented or
`
`published by others in the field, including the publications discussed in this
`
`petition. EX1002, ¶¶42-43; EX1003, ¶19.
`
`Typically, a person of ordinary skill in the relevant field as of the earliest
`
`alleged priority date, i.e., January 31, 2005, would have, or be a member of a team
`
`
`
`11
`
`
`
`with a member having, an advanced degree (e.g., a Ph.D.) in pharmacology, drug
`
`design and formulation, medicinal chemistry, or a related field. The skilled artisan
`
`may also have, or be a member of a team having, a medical degree (e.g., an M.D.)
`
`with experience treating thromboembolic disorders using anticoagulants.
`
`Alternatively, a person of ordinary skill in the relevant field might have less
`
`education but considerable professional experience in one or more of these fields.
`
`Dr. Leslie Z. Benet is a pharmacologist with more than 40 years of
`
`experience in drug research and clinical evaluation of drugs, including small
`
`molecule anticoagulants and vitamin K antagonists. EX1002, ¶¶1-2. Dr. Benet is a
`
`Professor of Pharmacology at the University of California, San Francisco where he
`
`teaches courses and publishes research on pharmacology, the in vivo
`
`pharmacokinetics and pharmacodynamics of drugs, as well as their metabolism and
`
`the implications for clinical drug development. EX1002, ¶¶3-4. Dr. Benet earned
`
`his Ph.D. in Pharmaceutical Chemistry from the University of California, San
`
`Francisco. EX1002, ¶2. Dr. Benet has authored or co-authored many peer-
`
`reviewed journal articles and book chapters and has been the recipient of numerous
`
`awards. Id. at ¶7. A summary of his education, experience, awards and honors,
`
`patents, publications, and presentations is provided in his CV, submitted as
`
`EX1046. See also EX1002, ¶¶1-11.
`
`
`
`12
`
`
`
`Dr. Benet is a well-qualified expert in the field of anticoagulation
`
`pharmacology and thus possesses the expertise necessary to determine and explain
`
`the level of ordinary skill in the art during the relevant time frame, i.e., prior to
`
`January 31, 2005.
`
`Dr. Neil E. Doherty is a clinician with more than 25 years of experience in
`
`the treatment of patients with thromboembolic disorders. EX1003, ¶¶1, 5. Dr.
`
`Doherty received his M.D. in 1982 from Harvard Medical School. EX1003, ¶2. Dr.
`
`Doherty was certified by the American Board of Internal Medicine in the
`
`subspecialty of Cardiovascular disease in 1991 and is a Fellow of the American
`
`College of Cardiology, the American College of Chest Physicians, and the
`
`American Society of Nuclear Cardiology. Id. at ¶¶3-4. A summary of his education
`
`and experience is provided in his CV, submitted as EX1052.
`
`II. GROUNDS FOR STANDING
`
`Petitioner certifies that, under 37 C.F.R. § 42.104(a), the ’218 patent is
`
`available for Inter Partes Review, and Petitioner is not barred or estopped from
`
`requesting Inter Partes Review of the ’218 patent on the grounds identified.
`
`III. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`
`Real Party-in-Interest (37 C.F.R. § 42.8(b)(1)): The following real parties-in-
`
`interest are identified: Mylan Pharmaceuticals Inc., which is the Petitioner in this
`
`matter and a wholly owned subsidiary of Mylan Inc.; Mylan Inc., which is an
`
`
`
`13
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`
`
`indirectly wholly owned subsidiary of Mylan N.V.; and, in an abundance of
`
`caution, Mylan N.V.
`
`Related Matters (37 C.F.R. § 42.8(b)(2)):
`
`Petitioner is involved in litigation over the ’218 patent in the action styled
`
`Bayer Intellectual Property GmbH v. Mylan Pharmaceuticals Inc., Case No. 1:17-
`
`cv-00584-RGA, filed by Bayer Intellectual Property GmbH et al. in the District of
`
`Delaware. A complaint asserting the ’218 patent against Petitioner was served no
`
`earlier than May 24, 2017. See EX1053; EX1065. Petitioner also identifies the
`
`following pending actions involving the ’218 patent: Bayer Intellectual Property
`
`GmbH v. Lupin Limited, 1:17-cv-01047, in the District of Delaware; Bayer
`
`Intellectual Property GmbH v. Breckenridge Pharmaceutical, Inc. 1:17-cv-01129;
`
`Bayer Intellectual Property GMBH v. InvaGen Pharmaceuticals, Inc., 1:17-cv-
`
`00812; Bayer Intellectual Property GmbH v. Alembic Pharmaceuticals Limited,
`
`1:17-cv-00675; Bayer Intellectual Property GmbH v. Sigmapharm Laboratories,
`
`LLC, 1:17-cv-00648; Bayer Intellectual Property GmbH v. Taro Pharmaceuticals
`
`Indus. Ltd., 1:17-cv-00462; and Bayer Intellectual Property GmbH v. Micro Labs
`
`Ltd., 1:17-cv-00560, in the District of Delaware.
`
`Lead and Back-Up Counsel (37 C.F.R. § 42.8(b) (3)):
`
`Lead Counsel: Steven W. Parmelee (Reg. No. 31,990)
`
`Back-Up Counsel: Michael T. Rosato (Reg. No. 52,182)
`
`
`
`14
`
`
`
`Back-Up Counsel: Jad A. Mills (Reg. No. 63,344)
`
`Service Information (37 C.F.R. § 42.8(b) (4)):
`
`Petitioner hereby consents to electronic service.
`
`Email: sparmelee@wsgr.com; mrosato@wsgr.com; jmills@wsgr.com
`
`Post: WILSON SONSINI GOODRICH & ROSATI
`
`701 Fifth Avenue, Suite 5100, Seattle, WA 98104-7036
`
`Tel.: 206-883-2542 Fax: 206-883-2699
`
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED
`
`A. Asserted Grounds of Unpatentability
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`Petitioners request review of claims 1-4 of the ’218 patent under 35 U.S.C. §
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`311 and AIA § 6 and that each of the claims be canceled as unpatentable based on
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`the following grounds of challenge:
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`Ground
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`Claims
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`Obvious under 35 U.S.C. §103 over:
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`1
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`2
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`1-4
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`1-4
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`The ’610 Publication and Kubitza Abstracts
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`The ’610 Publication, Kubitza Abstracts, and Forsman
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`B.
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`Evidence of Unpatentability Not Considered in Prosecution
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`This Petition presents new evidence not presented during prosecution or
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`before the Board in the earlier ex parte appeal. Specifically, the Board noted that
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`“based on the evidence of record, we cannot conclude that this disclosure [of
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`Kubitza 2] indicates a ‘rapid-release’ tablet as defined in the Specification.”
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`EX1004 at 0116-17. The Board also noted the Examiner had offered no
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`15
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`
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`explanation as to Kubitza 2 teaching or suggesting a rapid-release tablet in line
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`with its interpretation. Id. at 0117. Petitioner’s evidence presented in this Petition
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`establishes that a person of ordinary skill in the art would understand Kubitza
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`Abstracts as disclosing administration of a rapid-release tablet, that a POSA would
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`not understand the claim term rapid-release tablet as being limited to tablets having
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`a Q value (30 minutes) of 75%, and that administration of rivaroxaban in a rapid-
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`release tablet having a Q value (30 minutes) of 75% would have been obvious as of
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`January 2005. Thus, this Petition provides the Board with the information it did not
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`have before it during the ex parte appeal that conventional tablets, including those
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`in Kubitza, are rapid-release tablets.
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`To establish the meaning of rapid-release tablets in the ’218 patent as the
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`term would have been understood by a person of ordinary skill in view of the
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`specification, Petitioner provides the declarations of Dr. Leslie Z. Benet, Ph.D.,
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`and Dr. Neil E. Doherty, M.D. Each expert has decades of relevant experience.
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`EX1002, ¶¶12-13; EX1003, ¶¶6-7. As discussed above in Section I.D, Dr. Doherty
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`is a clinician with more than 25 years of experience in the treatment of patients
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`with thromboembolic disorders. Dr. Benet is a pharmacologist with more than 40
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`years of experience in drug research and clinical evaluation of drugs, including
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`small molecule anticoagulants and vitamin K antagonists. Indeed, the very
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`reference relied upon in the ’218 patent to establish unexpected results for once-
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`16
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`daily administration of rivaroxaban was a chapter in Goodman and Gilman written
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`by Dr. Benet. Dr. Benet’s testimony confirms that Patent Owner’s claim to
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`patentability of the claims of the ’218 are incorrect and read the cited prior art
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`references out of context.
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`Both Drs. Benet and Doherty confirm that the term rapid-release tablet, as
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`used in the claims of the ’218 patent in view of its specification, encompass the
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`types of rivaroxaban tablets disclosed in the ’610 publication and in the Kubitza
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`Abstracts. Their testimony is corroborated by at least three prior art references that
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`were not before the Patent Office during the prosecution of the ’218 patent
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`(EX1013 (Guidance for Industry, Center for Drug Evaluation and Research, 2002);
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`EX1032 (International Patent Publication No. WO 2003/101423 to Abrahmsén et
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`al.; EX1054 (Chapter 711 Dissolution, THE UNITED STATES PHARMACOPEIA (USP)
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`2000)), as well as a fourth prior art reference that was cited in an IDS but never
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`substantively discussed during prosecution (EX1014 (Aulton et al.,
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`PHARMACEUTICS: THE SCIENCE OF DOSAGE FORM DESIGN, 2nd Edition (2002))).
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`Moreover, both experts confirm that, even if the claims were read to be
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`limited to a rapid-release tablet having a Q value (30 minutes) of 75%, that such a
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`rapid-release tablet was obvious in view of the prior art. Their testimony is
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`corroborated by evidence that was not before the Patent Office during prosecution.
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`Indeed, neither the Examiner nor the Board considered the Forsman reference
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`17
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`(EX1007), which is asserted in Ground 2, nor the Abrahmsén reference (EX1032),
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`which is cited to support reasonable expectation of success in each of Grounds 1
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`and 2.
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`Because this petition and its supporting declarations present new evidence,
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`including testimonial evidence, demonstrating the unpatentability of the challenged
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`claims, the allowance of the claims during prosecution based on the limited
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`disclosure and discussion presented by Applicants should not receive deference by
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`the Board. See Unified Patents Inc. v. Berman, IPR2016-01571, Paper 10 at 13
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`(informative) (petitioner reliance on reference not listed on face of the patent,
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`much less used by Examiner as a ground of rejection, overcomes owner’s Section
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`325(d) argument for non-institution); Hospira, Inc. v. Genentech, Inc., IPR2017-
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`00739, Paper 16 at 17-18 (informative) (recognizing Office’s policy favoring
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`institution to correct “errors by the Office in allowing the patent” and to permit
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`petitioners to be heard, but exercising discretion because petitioner did not present
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`new argument or evidence indicating Examiner had erred during prosecution);
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`Kayak Software Corp. v. International Business Machines Corp., CBM2016-
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`00075, Paper 16 at 8-10 (informative) (noting that petitioner had not “brought
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`forward and explained some specific circumstances that have materially changed
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`or of which the Office was not aware of …such as, for example, changed claim
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`constructions,” which would have weighed in favor of institution).
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`18
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`Moreover, Petitioner has not previously filed a petition directed to any
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`claims of the ’218 patent, and is not aware of any petition for IPR previously
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`having been filed to challenge the claims of the ’218 patent. See General Plastic
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`Indus. Co., Ltd. V. Canon Kabushiki Kaisha, IPR2016-01357, -01358, -01359, -
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`01360, -01361, Paper 19, at 15-16 (precedential) (discussing factors often
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`considered in exercising discretion to institute when successive petitions are filed
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`regarding the same claims).
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`For the reasons discussed above and in the remainder of this Petition, the
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`Board should not deny institution under Section 325(d).
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`V. CLAIM CONSTRUCTION
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`In an inter partes review, a claim in an unexpired patent is given its broadest
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`reasonable construction in light of the specification. 37 C.F.R. § 42.100(b); Cuozzo
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`Speed Techs., LLC v. Lee, 579 U.S. ---, 136 S. Ct. 2131, 2146 (2016). Claim terms
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`are also “generally given their ordinary and customary meaning,” which is the
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`meaning that the term would have to a person of ordinary skill in the art at the time
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`of the priority date of the ’218 patent in view of the specification. In re Translogic
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`Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007); EX1002, ¶44; EX1003, ¶30.
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`Under either standard, there is a reasonable likelihood that Petitioner will prevail
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`with respect to the challenged claims.
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`19
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`The ’218 patent defines the term “treatment” to include therapeutic and
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`prophylactic treatment of thromboembolic disorders. EX1001, 7:25-26; EX1002,
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`¶45; EX1003, ¶¶21-22. Petitioner agrees with the Board’s conclusion during the
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`prosecution of the ’218 patent that the “method of treating a thromboembolic
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`disorder” as recited in the ’218 patent does not exclude scenarios where
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`rivaroxaban is administered to healthy individuals, who may also be in need of
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`prophylactic treatment for thromboembolic disorders. EX1004 at 0111 (FF2),
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`0115-16 (“Appellants’ Specification defines ‘treatment’ as including ‘prophylactic
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`treatment’ (FF2), i.e., administration to healthy people to prevent thromboembolic
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`disorders from developing.”); EX1002, ¶54.
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`Indeed, it was well known prior to January 2005 that venous thromboemboli
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`(“VTE”), including pulmonary emboli, deep vein thromboses, and stroke, can
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`occur in healthy individuals flying long distances on commercial airlines,
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`commonly described as “economy class syndrome.” For instance, a news article
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`published in 2004 explains that new guidelines released by the American College
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`of Chest Physicians “strongly advise all patients traveling on flights of more than
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`six hours” to take precautions to prevent “travel-related blood clots” such as “deep
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`vein thrombosis,” or a “potentially fatal pulmonary embolism.” EX1010 (Morales,
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`T., CBS NEWS, 2004) at 1-2; EX1003, ¶¶23-27. The article specifies age, obesity,
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`recent surgery, family history of blood clots, medical conditions or disease that
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`20
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`make a person susceptible to clotting, women who are pregnant or use
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`contraceptive pill or hormone replacement therapy as associated with “higher risk
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`for blood clots” and recommends that customers at greater risk for clots take “a
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`blood-thinning medication” prior to flying. Id.
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`Publications discussing the risk of thromboembolic disorders resulting from
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`flying were commonplace before 2005. See, e.g., EX1011 (Isayev et al., 58
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`NEUROL. (2002) 960-61) at 960-61 (discussing risk or stroke from economy class
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`syndrome); EX1012 (Foerch et al., 59 NEUROL. (2002) 962-63) at 962-63
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`(reporting economy class
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