UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________________________
`
`SAWAI USA, INC. AND
`SAWAI PHARMACEUTICAL CO., LTD.
`Petitioners,
`
`v.
`
`BIOGEN MA, INC.
`Patent Owner.
`_______________________________
`
`Patent No. 8,399,514
`_______________________________
`
`Inter Partes Review IPR2019-00789
`_______________________________
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,399,514
`
`
`
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`

`

`TABLE OF CONTENTS
`
`Page
`
`INTRODUCTION ........................................................................................... 1
`I.
`II. MANDATORY NOTICES ............................................................................. 1
`A.
`Real Parties-In-Interest (37 C.F.R. § 42.8 (b)(1)) ................................. 1
`B.
`Related Matters (37 C.F.R. § 42.8(b)(2)) .............................................. 2
`C.
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) ............................... 4
`D.
`Service Information (37 C.F.R. § 42.8(b)(4)) ....................................... 4
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.101 AND 42.104) ............... 4
`IV.
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED (37 C.F.R. § 42.22(A) AND 37
`C.F.R. § 42.104(B)) ......................................................................................... 5
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............... 6
`V.
`VI. STATEMENT OF THE REASONS FOR THE RELIEF REQUESTED ...... 7
`A.
`Summary of the Argument .................................................................... 7
`B.
`Level of Ordinary Skill in the Art .......................................................11
`C.
`The ’514 Patent and its Prosecution ....................................................11
`1.
`The Treatment of Multiple Sclerosis ........................................ 11
`2.
`The ’514 Patent ......................................................................... 12
`3.
`Prosecution of the ’514 Patent .................................................. 14
`Claim Construction (37 C.F.R. §§ 42.100(b), 42.104(b)(3)) ..............17
`Scope and Content of the Prior Art .....................................................18
`1.
`January 2006 Biogen Press Release .......................................... 18
`2.
`Schimrigk 2004 Abstract .......................................................... 19
`3.
`Kappos 2006 ............................................................................. 21
`4. WO ’342 .................................................................................... 22
`5.
`Clinical Trials ............................................................................ 23
`6.
`Joshi ’999 .................................................................................. 24
`7.
`ICH ............................................................................................ 25
`8.
`Prior Art Informing the General Knowledge of Ordinarily-
`Skilled Artisans ......................................................................... 25
`
`D.
`E.
`
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`

`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`F.
`
`3.
`
`2.
`
`Summary of Petitioner’s Obviousness Positions ................................26
`1.
`Law of Obviousness .................................................................. 26
`2.
`The Use of DMF to Treat Autoimmune Diseases, Such As MS,
`Was Well Known in the Art ...................................................... 28
`Skilled Artisans Would Have Been Motivated to Use 480
`mg/day of DMF to Treat MS with a Reasonable Expectation of
`Success ...................................................................................... 29
`G. Ground 1: Claims 1-20 Are Unpatentable As Obvious Over the
`January 2006 Biogen Press Release in View of the Schimrigk
`2004 Abstract. .....................................................................................35
`1.
`Independent Claims 1, 11, 15, and 20 are Obvious Over the
`January 2006 Biogen Press Release in View of the Schimrigk
`2004 Abstract. ........................................................................... 35
`The Dependent Claims of the ’514 Patent are Obvious Over the
`January 2006 Biogen Press Release in View of the Schimrigk
`2004 Abstract. ........................................................................... 39
`H. Ground 2: Claims 1-20 Are Unpatentable As Obvious over
`Kappos 2006 in view of the Schimrigk 2004 Abstract. ......................44
`1.
`Independent Claims 1, 11, 15, and 20 are Obvious over Kappos
`2006 in view of the Schimrigk 2004 Abstract. ......................... 45
`The Dependent Claims are Obvious over Kappos 2006 Press
`Release in view of the Schimrigk 2004 Abstract. ..................... 48
`Ground 3: Claims 1-20 Are Unpatentable As Obvious over
`Kappos 2006 in View of WO ’342. ....................................................48
`1.
`Independent Claims 1, 11, 15, and 20 are Obvious over Kappos
`2006 in view of WO ’342. ........................................................ 48
`The Dependent Claims are Obvious over Kappos 2006 in View
`of WO ’342. .............................................................................. 50
`Ground 4: Claims 1-20 are Unpatentable as Obvious Over
`Kappos 2006, Clinical Trials, Joshi ’999, and ICH ............................51
`1.
`Independent Claims 1, 11, 15, and 20 are obvious over Kappos
`2006, Clinical Trials, Joshi ’999, and ICH ............................... 51
`
`2.
`
`2.
`
`I.
`
`J.
`
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`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`2.
`
`The Dependent Claims are Obvious Over Kappos 2006,
`Clinical Trials, Joshi ’999, and ICH ......................................... 53
`K. Any Purported Secondary Considerations Fail to Overcome
`Prima Facie Obviousness ...................................................................53
`1.
`The Methods Recited in the ’514 Patent Produced No
`Unexpected Results. .................................................................. 54
`The ’514 Patent Satisfied No Long-Felt But Unmet Need. ...... 60
`Industry Praise Does Not Overcome Prima Facie
`Obviousness. ............................................................................. 61
`This Petition Should Not Be Denied Institution under § 325(d) ........61
`L.
`VII. CONCLUSION ..............................................................................................66
`
`
`2.
`3.
`
`137829457v2
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`

`TABLE OF AUTHORITIES
`
`Page
`
`Cases
`
`Becton, Dickinson and Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Decision, Paper No. 8.............................................................. 64
`
`Becton, Dickson and Co.,
`IPR2017-01586, Paper 8 ..................................................................................... 63
`
`Boehringer Ingelheim Pharms., Inc. v. Genetech, Inc.,
`IPR2017-02031, 2018 WL 1605267 (PTAB Mar. 29, 2018) ............................. 65
`
`In re Boesch,
`617 F.2d 272 (C.C.P.A. 1980) ............................................................................ 27
`
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016) ........................................................................................ 17
`
`Enova Tech. Corp. v. Seagate Tech. (US) Holdings Inc.,
`706 F. App’x 987 (Fed. Cir. 2017) ..................................................................... 61
`
`Galderma Labs., L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) ............................................................................ 61
`
`General Plastic Indus. Co. v. Canon Kabushiki Kaisha,
`IPR2016-01357, Paper 19 ..................................................................................... 7
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ............................................................................................ 27
`
`Merck Sharp & Dohme Corp. v. Pfizer Inc.,
`IPR2017-02138, 2018 WL 1475743 (PTAB Mar. 22, 2018) ............................. 65
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .......................................................................... 53
`
`Pfizer, Inc. v. Biogen, Inc.,
`IPR2018-00285, Paper 10 ..................................................................................... 7
`
`Pfizer, Inc. v. Genentech, Inc.,
`IPR2017-01923, 2018 WL 1666694 (PTAB Apr. 4, 2018) ............................... 66
`
`137829457v2
`
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`
`

`

`TABLE OF AUTHORITIES
`(continued)
`
`Page
`
`Reckitt Benckiser Pharm. Inc. v. Watson Labs., Inc.,
`C.A. Nos. 13-1674-RGA, 14-422-RGA, 2016 WL 3186659 (D.
`Del. June 3, 2016) ............................................................................................... 27
`
`Statutes
`
`35 U.S.C. § 102(a) ....................................................................................... 22, 23, 26
`
`35 U.S.C. § 102(b) ............................................................................................passim
`
`35 U.S.C. § 102(e) ............................................................................................. 23, 25
`
`35 U.S.C. § 103(a) ............................................................................................. 14, 27
`
`35 U.S.C. §§ 311-319................................................................................................. 1
`
`35 U.S.C. § 314(a) ..................................................................................................... 6
`
`35 U.S.C. § 325(d) ................................................................................................... 61
`
`
`
`137829457v2
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`

`
`
`EXHIBIT
`NO.
`
`LIST OF EXHIBITS
`
`DESCRIPTION
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`U.S. Patent No. 8,399,514, Treatment for Multiple
`Sclerosis (filed Feb. 13, 2012) (issued Mar. 19, 2013)
`
`Declaration of John R. Corboy, M.D.
`
`Declaration of Leslie Benet, Ph.D.
`
`Declaration of Ian McKeague, Ph.D.
`
`Biogen News Release, Phase II Study of Oral Compound
`BG-12 Meets Primary Endpoint in Multiple Sclerosis (Jan. 9,
`2006)
`
`S. Schimrigk et al., A Prospective, Open-Label, Phase II
`Study of Oral Fumarate Therapy for the Treatment of
`Relapsing-Remitting Multiple Sclerosis, 10 (Suppl. 2)
`MULTIPLE SCLEROSIS CLIN. & LAB. RES. S258, Abstract
`P642 (2004)
`
`L. Kappos et al., Efficacy of a Novel Oral Single-Agent
`Fumarate, BG00012, in Patients with Relapsing-Remitting
`Multiple Sclerosis: Results of a Phase 2 Study, 253 (Suppl.
`2) J. NEUROL. II27, O108 (2006)
`
`International Publication No. WO 2006/0037342 A2
`(published Apr. 13, 2006)
`
`U.S. Patent No. 7,320,999, Dimethyl Fumarate for the
`Treatment of Multiple Sclerosis (filed July 17, 2002)
`(issued Jan. 22, 2008)
`
`NCT00168701, CLINICALTRIALS.GOV,
`https://clinicaltrials.gov/ archive/NCT00168701/2005_09_14
`
`ICH HARMOISED TRIPARITE GUIDELINE – DOSE-RESPONSE
`INFORMATION TO SUPPORT DRUG REGISTRATION E4 (Mar. 10,
`1994)
`
`137829457v2
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`
`

`

`LIST OF EXHIBITS
`(continued)
`
`EXHIBIT
`NO.
`
`DESCRIPTION
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`S. Schimrigk et al., A Prospective, Open-Label, Phase II
`Study of Oral Fumarate Therapy for the Treatment of
`Relapsing-Remitting Multiple Sclerosis (2004), available at
`http://web.archive.org/web/
`20041021033354/http://www.fumapharm.ch:80/pdf/BG-12_
`Schimrigk_Poster_Final.pdf (“Schimrigk 2004 Poster”)
`
`N. Brune et al., Oral Fumarate Therapy Alters Cytokine
`Production in Patients with Relapsing-Remitting Multiple
`Sclerosis, 10 (suppl. 2) MULTIPLE SCLEROSIS CLIN & LAB.
`RES. S259, ABSTRACT P643 (2004)
`
`S. Schimrigk et al., An Open-Label, Prospective Study of
`Oral Fumaric Acid Therapy for the Treatment Relapsing-
`Remitting Multiple Sclerosis (RRMS), 64(6)(Suppl. 1)
`NEUROLOGY A392, S46.003 (2005)
`
`L. Kappos et al., A Randomised, Placebo-controlled Phase II
`Trial of a Novel Oral Single-Agent Fumarate Therapy,
`BG00012, in Patients with Relapsing-Remitting Multiple
`Sclerosis, 252 (Suppl. 2) J. NEUROL. II/148, P574 (2005)
`
`Biogen News Release, Oral Compound BG-12 Achieves
`Primary Endpoint in Phase II Study of Relapsing-Remitting
`Multiple Sclerosis; Treatment with BG-12 Led to Statistically
`Significant Reductions in MRI Measures (May 30, 2006)
`
`C. Nieboer et al., Fumaric Acid Therapy in Psoriasis: A
`Double-Blind Comparison between Fumaric Acid Compound
`Therapy and Monotherapy with Dimethylfumaric Acid Ester,
`181 DERMATOLOGICA 33 (1990)
`
`S. Schimrigk et al., Oral Fumaric Acid Esters for the
`Treatment of Active Multiple Sclerosis: An Open-Label,
`Baseline-Controlled Pilot Study, 13 EUR. J. NEUOL. 604
`(2006)
`
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`

`

`EXHIBIT
`NO.
`
`1019
`
`LIST OF EXHIBITS
`(continued)
`
`DESCRIPTION
`
`U. Mrowietz et al., Dimethylfumarate for Psoriasis: More
`than a Dietary Curiosity, 11(1) TRENDS MOL. MED. 43
`(2005)
`
`1020
`
`Fumaderm® prescribing information
`
`1021
`
`H.M. Ockenfels et al., The Antipsoriatic Agent
`Dimethylfumarate Immunomodulates T-Cell Cytokine
`Secretion and Inhibits Cytokines of the Psoriatic Cytokine
`Network, 139 BR. J. DERM. 390 (1998)
`
`1022
`
`INTENTIONALLY LEFT BLANK
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`R. de Jong et al., Selective Stimulation of T Helper 2
`Cytokine Responses by the Anti-Psoriasis Agent
`Monomethylfumarate, 26 EUR. J. IMMUNOL. 2067 (1996)
`
`P. Nibbering et al., Effects of Monomethylfumarate on
`Human Granulocytes, 101 J. INVEST. DERMATOL. 37 (1993)
`
`U.S. Patent No. 6,509,376, Utilization of Dialkyfumarates
`(filed Oct. 29, 1999) (issued Jan 21, 2003)
`
`Biogen News Release, BG-12 Psoriasis Study Meets Primary
`Endpoint; Oral Compound Also Being Studied for MS in
`Phase II Trial (Apr. 7, 2005)
`
`A.D. Ormerod et al., Fumaric Acid Esters, Their Place in the
`Treatment of Psoriasis, 150 Br. J. Dermatol. 630 (2004)
`
`U. Mrowietz et al., Treatment of Psoriasis with Fumaric Acid
`Esters: Results of a Prospective Multicentre Study,
`138(3) BR. J. DERMATOL. 456 (1998)
`
`W. Nugteren-Huying et al., Fumaric Acid Therapy for
`Psoriasis: A Randomized, Double-Blind, Placebo-
`Controlled Study,” 22(2) J. AM. ACAD. DERMATOL. 311
`(1990)
`
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`

`LIST OF EXHIBITS
`(continued)
`
`EXHIBIT
`NO.
`
`DESCRIPTION
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`P. Altmeyer et al., Antipsoriatic Effect of Fumaric Acid
`Derivatives: Results of a Multicenter Double-Blind Study in
`100 Patients, 30 J. AM. ACAD. DERMATOL. 977 (1994)
`
`C. Nieboer et al., Systemic Therapy with Fumaric Acid
`Derivatives: New Possibilities in the Treatment of Psoriasis,
`20 J. AM. ACAD. DERM. 601 (1989)
`
`N. Brune et al., Detection of Altered Intracellular TH1- and
`TH2-Type Cytokine Production of Peripheral Blood
`Mononuclear cells (PBMCs) in Patients with Relapsing-
`Remitting Multiple Sclerosis (RRMS) Undergoing an Oral
`Fumaric-Acid Ester Therapy, 4(4) MULTIPLE SCLEROSIS:
`CLINICAL AND LABORATORY RESEARCH P3038 (1998)
`(ECTRIMS 98:14th Congress of the European Committee for
`Treatment and Research in Multiple Sclerosis, Sept. 9-12,
`1998, Stockholm, Sweden)
`
`S. Schimrigk et al., Oral Fumaric Acid Ester (FAE) in
`Relapsing-Remitting Multiple Sclerosis (RRMS). A Short
`Term, Open, clinical, Immunological and Magnetic
`Resonance Imaging (MRI) Controlled Phase II Trial, 246
`(Suppl. 1) J. NEUROL. I/36, 144 (1999) (Ninth Meeting of the
`European Neurological Society, June 5-9, 1999, Milan, Italy)
`
`L. Kappos et al., A Randomized, Placebo-Controlled Phase 2
`Trial of a Novel Oral Fumarate, BG00012, in Patients with
`Relapsing-Remitting Multiple Sclerosis (15th Meeting of the
`European Neurological Society, June 18-22, 2005), and
`Declaration of Gilmore O’Neill, M.D.
`
`A. Wierinckx et al., Detoxication Enzyme Inducers Modify
`Cytokine Production in Rat Mixed Glial Cells, 166 J.
`NEUROIMMUNOL. 132 (2005)
`
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`
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`

`LIST OF EXHIBITS
`(continued)
`
`EXHIBIT
`NO.
`
`DESCRIPTION
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`R. Fox et al., Dimethyl Fumarate to Treat Multiple Sclerosis,
`in MULTIPLE SCLEROSIS THERAPEUTICS 387 (Jeffrey A.
`Cohen et al. eds., 4th ed. 2011)
`
`European Medicines Agency, Assessment Report, Tecfidera
`(Nov. 26, 2013)
`
`R. Gold et al., Placebo-Controlled Phase 3 Study of Oral
`BG-12 for Relapsing Multiple Sclerosis, 367 NEW ENG. J.
`MED. 1098 (2012) (“Define Study”)
`
`R. Fox et al., Placebo-Controlled Phase 3 Study of Oral BG-
`12 or Glatiramer in Multiple Sclerosis, 367 NEW ENG. J.
`MED. 1087 (2012) (“Confirm Study”)
`
`E. Frohman et al., Multiple Sclerosis - The Plaque and its
`Pathogenesis, 354 NEW ENG. J. MED. 942 (2006)
`
`J. Miller, The Importance of Early Diagnosis of Multiple
`Sclerosis, 10(3) J. MANAG. CARE PHARM. S4 (2004)
`
`MS Prevalence, NATIONALMSSOCIETY.ORG,
`https://www.nationalmssociety.org/About-the-Society/MS-
`Prevalence (last visited July 9, 2018)
`
`S. Rich et al., Stepped-Care Approach to Treating MS: A
`Managed Care Treatment Algorithm, 10(3) J. MANAG. CARE
`PHARM. S26 (2004)
`
`D. Meier et al., Monitoring Treatment Efficacy with
`Magnetic Resonance Imaging (MRI) in an Open Phase II
`Study with Fumaric-Acid Esters (Fumaderm®) in Patients
`with relapsing-Remitting MS (RRMS), 4(4) MULTIPLE
`SCLEROSIS: CLINICAL AND LABORATORY RESEARCH P3037
`(1998) (ECTRIMS 98:14th Congress of the European
`Committee for Treatment and Research in Multiple Sclerosis,
`Sept. 9-12, 1998, Stockholm, Sweden)
`
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`

`LIST OF EXHIBITS
`(continued)
`
`EXHIBIT
`NO.
`
`DESCRIPTION
`
`N. Brune et al., Oral Fumaric-Acid Ester Therapy (FAE)
`Influence T-Helper Cell Apoptosis in Peripheral Blood
`Lymphocytes (PBLS) and Soluble Intercellular Adhesion
`Molecule-I (SICAM-1) in Serum of Patients with Relapsing-
`Remitting Multiple Sclerosis (RRMS), 246 (Suppl. 1) J.
`NEUROL. I/61, P272 (1999) (Ninth Meeting of the European
`Neurological Society, June 5-9, 1999, Milan, Italy)
`
`L. Kappos et al., Efficacy of a Novel Oral Single-Agent
`Fumarate, BG00012, in Patients with Relapsing-Remitting
`Multiple Sclerosis: Results of a Phase II Study (16th
`Meeting of the European Neurological Society, May 30,
`2006) attached as Exhibit C to the Declaration of Katherine
`T. Dawson in Biogen U.S. Patent App. No. 12/526,296 and
`marked as Ex. 1018 in Biogen MA Inc. v. Forward Pharma
`A/S, Interference No. 106,023 (“Kappos 2006 Presentation”)
`
`Leon Shargel et al., APPLIED BIOPHARMACEUTICS &
`PHARMAKINETICS 575-611 (5th ed. 2005)
`
`L. Kappos et al., Efficacy and Safety of Oral Fumarate in
`Patients with Relapsing-Remitting Multiple Sclerosis: A
`Multicentre, Randomised, Double-Blind, Placebo-Controlled
`Phase IIb Study, 372 LANCET 1463 (2008)
`
`FDA GUIDANCE FOR INDUSTRY - NON-INFERIORITY CLINICAL
`TRIALS TO ESTABLISH EFFECTIVENESS (Nov. 2016)
`
`E. de Klerk et al., Patient Compliance in Rheumatoid
`Arthritis, Polymyalgia Rheumatica, and Gout, 30 J.
`RHEUMATOLOGY 44 (2003)
`
`A. Paes et al., Impact of Dosage Frequency on Patient
`Compliance, 20(10) DIABETES CARE 1512 (1997)
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`1050
`
`1051
`
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`

`LIST OF EXHIBITS
`(continued)
`
`EXHIBIT
`NO.
`
`DESCRIPTION
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058
`
`1059
`
`
`
`S. Eisen et al., The Effect of Prescribed Daily Dose
`Frequency on Patient Medication Compliance, 150 ARCH.
`INTERN. MED. 1881 (1990)
`
`Prosecution History Excerpts, U.S. Patent No. 8,399,514
`
`Declaration of Robert Mihail
`
`Declaration of Jennifer Rock
`
`Declaration of Robert Walter Baumhefner, M.D.
`
`Declaration of Jacquelyn Bainbridge, Pharm.D.
`
`Declaration of Ronald G. Marks, Ph.D.
`
`Declaration of Jennifer Rock
`
`137829457v2
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`

`
`
`I.
`
`INTRODUCTION
`
`Sawai USA, Inc. and Sawai Pharmaceutical Co., Ltd. (“Petitioners”) petition
`
`for Inter Partes Review of claims 1-20 of U.S. Patent No. 8,399,514 (“the ‘514
`
`patent”) (Ex. 1001), which is assigned to Biogen MA Inc. (“Patent Owner”), under
`
`35 U.S.C. §§ 311-319 and 37 C.F.R. § 42 and seeks a determination that all claims
`
`(1-20) of the ’514 patent be canceled as unpatentable.
`
`This Petition is filed in accordance with 37 C.F.R. § 42.106(a). Filed herewith
`
`is a power of attorney and exhibit list per § 42.10(b) and § 42.63(e). Pursuant to
`
`37 C.F.R. § 42.103, the fee set forth in § 42.15(e) accompanies this Petition. Inter
`
`partes review of claims 1-20 the ’514 patent was instituted in IPR2018-01403 on
`
`February 6, 2019, based on a petition filed by Mylan Pharmaceuticals, Inc.
`
`(“Mylan”). For the sake of completeness and efficiency, the present Petition is a
`
`practical copy of the petition in IPR2018-01403, updated with identifying
`
`information regarding the present petitioner. A motion for Joinder with IPR2018-
`
`01403 is being filed concurrently with this Petition.
`
`II. MANDATORY NOTICES
`
`A.
`
`Real Parties-In-Interest (37 C.F.R. § 42.8 (b)(1))
`
`The real parties-in-interest for Petitioners are Sawai USA, Inc., Sawai
`
`Pharmaceutical Co., Ltd., Sawai America Holdings Inc., Sawai America, LLC,
`
`Upsher-Smith Laboratories LLC, and Stason Pharmaceuticals, Inc.
`
`137829457v2
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`
`

`

`
`
`B.
`
`Related Matters (37 C.F.R. § 42.8(b)(2))
`
`Petitioners are not aware of any reexamination certificates or pending
`
`prosecution concerning the ’514 patent. Petitioners are defendants to the following
`
`litigation involving the ’514 patent:
`
`Biogen Int’l GmbH v. Sawai USA, Inc., C.A. No. 17-cv-00875 (D. Del.).
`
`Other pending litigations involving the ’514 patent: Biogen Int’l GmbH v.
`
`Amneal Pharms LLC, C.A. No. 17-cv-00823-LPS (consolidated) (D. Del.); Biogen
`
`MA Inc. v. Caribe Holdings (Cayman) Co. Ltd., C.A. No. 18-cv-00121-LPS (D.
`
`Del.); Biogen Int’l GmbH v. Banner Life Sciences LLC, C.A. No. 18-cv-00582-LPS
`
`(D. Del.); Biogen Int’l GmbH v. Sandoz Inc., C.A. No. 17-cv-00874-LPS (D. Del.);
`
`Biogen Int’l GmbH v. Accord Healthcare Inc., C.A. No. 17-cv-00872-LPS (D. Del.);
`
`Biogen Int’l GmbH v. Mylan Pharm. Inc., C.A. No. 17-cv-116-IMK (N.D.W. Va.);
`
`Biogen MA Inc. v. Shipla Medicare Ltd., C.A. No. 17-cv-00847-LPS (D. Del.);
`
`Biogen MA Inc. v. Sun Pharma Global FZE, C.A. No. 17-cv-00848-LPS (D. Del.);
`
`Biogen MA Inc. v. Windlas Healthcare, Pvt. Ltd., C.A. No. 17-cv-00849-LPS (D.
`
`Del.); Biogen Int’l GmbH v. Alkem Labs Ltd., , C.A. No. 17-cv-00850-LPS (D. Del.);
`
`Biogen Int’l GmbH v. Cipla Ltd., C.A. No. 17-cv-00851-LPS (D. Del.); Biogen Int’l
`
`GmbH v. Glenmark Pharm. Ltd., C.A. No. 17-cv-00852-LPS (D. Del.); Biogen Int’l
`
`GmbH v. Lupin Atlantis Holdings SA, C.A. No. 17-cv-00853-LPS (D. Del.); Biogen
`
`Int’l GmbH v. Torrent Pharm. Ltd., C.A. No. 17-cv-00854-LPS (D. Del.); Biogen
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`Int’l GmbH v. Pharmathen S.A., C.A. No. 17-cv-00855-LPS (D. Del.); Biogen Int’l
`
`GmbH v. Twi Pharms., Inc., C.A. No. 17-cv-00856-LPS (D. Del.); Biogen Int’l
`
`GmbH v. Macleods Pharm., Ltd., C.A. No. 17-cv-00857-LPS (D. Del.); Biogen MA
`
`Inc. v. Graviti Pharms. Pvt. Ltd., 17-cv-00846-LPS (D. Del.); Biogen Int’l GmbH v.
`
`MSN Labs. Pvt. Ltd., C.A. No. 17-cv-00845-LPS (D. Del.); Biogen Int’l GmbH v.
`
`Zydus Pharms. (USA) Inc., C.A. No. 17-cv-00954-LPS (D. Del.); Biogen Int’l
`
`GmbH v. Banner Life Sciences LLC, C.A. No. 18-cv-00582-LPS (D. Del.); Biogen
`
`Int’l GmbH v. Aurobindo Pharma U.S.A., Inc., C.A. No. 17-cv-00824-LPS (D. Del.);
`
`Biogen Int’l GmbH v. Hetero USA Inc., C.A. No. 17-cv-00825-LPS (D. Del.);
`
`Biogen MA Inc. v. Impax Labs., Inc., C.A. No. 17-cv-00826-LPS (D. Del.); Biogen
`
`MA Inc. v. Prinston Pharm. Inc., C.A. No. 17-cv-00827-LPS (D. Del.); Biogen MA
`
`Inc. v. Slayback Pharma LLC, C.A. No. 17-cv-00828-LPS (D. Del.).
`
`Other proceedings in front of the Patent Trial and Appeal Board include:
`
`Coalition for Affordable Drugs V LLC v. Biogen MA Inc., IPR2015-01993;
`
`Coalition for Affordable Drugs V LLC v. Biogen MA Inc., IPR2015-01136; Biogen
`
`MA Inc., v. Forward Pharma A/S, Patent Interference 106,023; Mylan
`
`Pharmaceuticals Inc. v. Biogen MA Inc., IPR2018-01403. In IPR2018-01403, the
`
`Board has already instituted trial for all claims of the ’514 patent on each of the
`
`grounds raised herein.
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`Patent applications in the same patent family are pending as U.S. Patent
`
`Application Nos. 16/221,172 and 16/238,724.
`
`C.
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3))
`
`Lead Counsel
`
`Brian Sodikoff
`Reg. No. 54,697
`Katten Muchin Rosenman LLP
`525 West Monroe Street
`Chicago, IL 60661-3693
`brian.sodikoff@kattenlaw.com
`
`
`Back-Up Counsel
`Christopher B. Ferenc
`Reg. No. 59,365
`Katten Muchin Rosenman LLP
`2900 K Street NW
`North Tower - Suite 200
`Washington, DC 20007-5118
`christopher.ferenc@kattenlaw.com
`
`
`
`
`D.
`
`Service Information (37 C.F.R. § 42.8(b)(4))
`
`Petitioners respectfully request that all correspondence be directed to lead
`
`counsel and back-up counsel at the contact information provided above. Petitioners
`
`consent to electronic service by e-mail at the following email addresses:
`
`brian.sodikoff@kattenlaw.com; and
`
`christopher.ferenc@kattenlaw.com.
`
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.101 AND 42.104)
`
`Pursuant to 37 C.F.R. § 42.104(a), Petitioners certify that the ’514 patent is
`
`available for inter partes review and that the Petitioners are not barred or estopped
`
`from requesting inter partes review on the grounds identified herein.
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`IV.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED (37 C.F.R. § 42.22(A) AND 37 C.F.R.
`§ 42.104(B))
`
`Petitioners respectfully request inter partes review and cancellation of
`
`claims 1-20 on the grounds set forth below.
`
`Ground 1: Claims 1-20 are obvious over the January 2006 Biogen Press
`
`Release in view of the Schimrigk 2004 Abstract.
`
`Ground 2: Claims 1-20 are obvious over Kappos 2006 in view of the
`
`Schimrigk 2004 Abstract.
`
`Ground 3: Claims 1-20 are obvious over Kappos 2006 in view of WO ’342.
`
`Ground 4: Claims 1-20 are obvious over Kappos 2006, Clinical Trials, Joshi
`
`’999, and ICH.
`
`Petitioners’ full statement of the reasons for the relief is set forth below. In
`
`support of these grounds for unpatentability, Petitioners submit the expert
`
`declarations of Dr. John Corboy (Ex. 1002 (“Corboy Decl.”)), Dr. Leslie Benet
`
`(Ex. 1003 (“Benet Decl.”)), Dr. Ian McKeague (Ex. 1004 (“McKeague Decl.”)), Dr.
`
`Robert Baumhefner (Ex. 1056 (“Baumhefner Decl.”)), Dr. Jacquelyn Bainbridge
`
`(Ex. 1057 (“Bainbridge Decl.”)), and Dr. Ronald Marks (Ex. 1058 (“Marks Decl.”)),
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`and also relies on other Exhibits set forth in the concurrently-filed Listing of
`
`Exhibits.1
`
`V.
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`A petition for inter partes review must demonstrate a “reasonable likelihood
`
`that the petitioner would prevail with respect to at least 1 of the claims challenged
`
`in the petition.” 35 U.S.C. § 314(a). This Petition clears that threshold. There is a
`
`reasonable likelihood that Petitioners will prevail with respect to at least one of the
`
`challenged claims. Moreover, it would be an inappropriate exercise of the Board’s
`
`discretion to deny institution here under § 314(a). First, Petitioners have not
`
`previously filed a petition for inter partes review of the ’514 patent. Moreover, the
`
`timing of this Petition does not suggest any delay by Petitioners; Petitioners were
`
`not involved in the earlier petitions filed by the Coalition for Affordable Drugs.
`
`Petitioners have filed this Petition within the statutory time frame for filing its
`
`
`1 Dr. Baumhefner’s (Ex. 1056), Dr. Bainbridge’s (Ex. 1057), and Dr. Marks’ (Ex.
`
`1058) declarations in support of these grounds is substantively identical to that of
`
`Dr. John R. Corboy’s (Ex. 1002), Dr. Leslie Z. Benet’s (Ex. 1003), and Dr. Ian
`
`McKeague’s (Ex. 1004) expert declarations, respectively, in the Mylan IPR. For
`
`simplicity, the corresponding declarations are cited in tandem, e.g., Ex. 1002/1056,
`
`Ex. 1003/1057, Ex. 1004/1058.
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`Petition asserting additional arguments and evidence. See General Plastic Indus.
`
`Co. v. Canon Kabushiki Kaisha, IPR2016-01357, Paper 19; see also e.g., Pfizer, Inc.
`
`v. Biogen, Inc., IPR2018-00285, Paper 10 at 22-25.
`
`VI.
`
`STATEMENT OF THE REASONS FOR THE RELIEF REQUESTED
`
`A.
`
`Summary of the Argument
`
`The claims of the ’514 patent are directed towards treating multiple sclerosis
`
`(“MS”) with 480 mg/day of dimethyl fumarate (“DMF”). The treatment of MS with
`
`DMF is nothing new; skilled artisans had known for years prior to the earliest
`
`priority date of the ’514 patent that DMF was an efficacious MS treatment. To
`
`extend patent protection on DMF for the treatment of MS, Patent Owner simply
`
`chose a dose—480 mg/day—that fell squarely within a predictable range of
`
`efficacious doses, and claimed that it “unexpectedly” achieved similar efficacy to
`
`the existing 720 mg/day DMF dose that was known to be efficacious. While Patent
`
`Owner’s alleged unexpected results argument caused the Board to find the
`
`’514 patent claims not unpatentable when the argument went unrebutted in a petition
`
`by the Coalition for Affordable Drugs, this Petition provides new evidence that
`
`proves skilled artisans would have expected efficacy. As detailed below, Biogen’s
`
`unexpected results argument rests on a faulty premise: that 360 mg/day of DMF is
`
`not efficacious. This Petition demonstrates that is not so, and the wealth of data
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`available to skilled artisans would have led them directly to dosing DMF at
`
`480 mg/day.
`
`DMF has been studied extensively and used since the 1990s. DMF was used
`
`in combination with monoethyl fumarate (MEF) salts, a composition known as
`
`Fumaderm®. Fumaderm® has been commercially available in Germany since the
`
`1990s, and is a well-known treatment for psoriasis. Like MS, psoriasis is an
`
`autoimmune disease. Studies throughout the 1990s also demonstrated that DMF is
`
`the most active component in Fumaderm®. Skilled artisans believed that MEF salts
`
`(Fumaderm®’s other component) provided little efficacy. Prior art studies also
`
`demonstrated that a 480 mg/day dose of DMF was effective to treat psoriasis.
`
`During the early 2000s, skilled artisans investigated treating MS with
`
`Fumaderm®, because of certain similarities between MS and psoriasis.
`
`Unsurprisingly, Fumaderm® was found to be an MS effective treatment in a prior
`
`art study by Schimrigk. Schimrigk found that Fumaderm® doses containing
`
`360 mg/day and 720 mg/day of DMF were effective to treat MS. Skilled artisans
`
`also knew that DMF was associated with certain bothersome dose-dependent side
`
`effects, such as flushing and gastrointestinal issues.
`
`In the mid-2000s, Biogen conducted a clinical trial to gain approval to market
`
`DMF to treat MS. This study (the “Kappos study” or the “phase II study”) tested
`
`DMF at concentrations of 120 mg/day (once daily), 360 mg/day (three times daily)
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`and 720 mg/day (three times daily). Given the wealth of knowledge skilled artisans
`
`had before the Kappos study, it was not surprising that in January 2006 Biogen
`
`announced in a press release that its trial had successfully met its primary endpoint.
`
`In May 2006, Kappos published an abstract and presented his study results.
`
`He reported that the 720 mg/day DMF dose demonstrated a “statistically significant
`
`response” and that the response was “dose-dependent.” Again, none of this was
`
`surprising given skilled artisans’ knowledge about the efficacy of DMF in treating
`
`MS. Taking this knowledge, together with DMF’s well-known side-effect profile, a
`
`skilled artisan would have had all she needed to optimize the DMF dose. A dose of
`
`480 mg/day was well within the predictably efficacious range of doses in MS; had
`
`been shown previously to be effective in treating psoriasis; would have been
`
`expected to improve the tolerability of DMF therapy; and was simple to administer
`
`twice a day, and thereby expected to improve compliance versus typical thrice daily
`
`dosing.
`
`Biogen argued extensively during examination and before this Board that it
`
`was “unexpected” that 480 mg/day DMF exhibited similar efficacy to 720 mg/day
`
`DMF. In a May 2006 Press Release reporting on the Kappos study, Biogen stated
`
`that the 360 mg/day dose did not achieve “statistically significant” efficacy versus
`
`placebo. Based on that finding, Biogen argued that it is surprising that 480 mg/day
`
`is as efficacious as 720 mg/day because 480 is numerically closer to 360 than to 720.
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`That argument is legally and scientifically unsound, and ignores data suggesting
`
`360 mg/day is an efficacious dose.
`
`Wh