`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________
`
`
`COALITION FOR AFFORDABLE DRUGS V LLC;
`HAYMAN CREDES MASTER FUND, L.P.;
`HAYMAN ORANGE FUND SPC – PORTFOLIO A;
`HAYMAN CAPITAL MASTER FUND, L.P.;
`HAYMAN CAPITAL MANAGEMENT, L.P.;
`HAYMAN OFFSHORE MANAGEMENT, INC.;
`HAYMAN INVESTMENTS, LLC;
`NXN PARTNERS, LLC;
`IP NAVIGATION GROUP, LLC;
`J KYLE BASS; and ERICH SPANGENBERG,
`Petitioner,
`
`v.
`
`BIOGEN MA INC.,
`Patent Owner.
`
`____________________________________________
`
`Case: IPR2015-01993
`U.S. Patent No. 8,399,514
`____________________________________________
`
`BIOGEN’S OPPOSITION TO THE PETITION
`
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`Page 1 of 65
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`Biogen Exhibit 2033
`Mylan v. Biogen
`IPR2018-01403
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`
`
`
`I.
`
`II.
`
`
`
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`Case No. IPR2015-01993
`Patent 8,399,514
`
`TABLE OF CONTENTS
`
`Introduction ...................................................................................................... 1
`
`Petitioner’s Definition of a Person of Ordinary Skill is Overly Broad ........... 4
`
`III. Biogen Is Entitled to the Filing Date of Its Provisional Application .............. 5
`
`A.
`
`The Provisional Application Provides Written Description
`Support for and Enables the ’514 Patent Claims .................................. 7
`
`1.
`
`2.
`
`The Provisional Application Provides Written
`Description Support for the ’514 Patent Claims ......................... 7
`
`Atofina Does Not Affect Biogen’s Entitlement to Priority ....... 10
`
`a.
`
`b.
`
`Atofina Applies Only Within the Limited Context
`of Anticipation ................................................................ 11
`
`Atofina Does Not Apply to Written Description ............ 13
`
`3.
`
`The Provisional Application Enables the ’514 Patent
`Claims ....................................................................................... 14
`
`B.
`
`The Remaining Requirements of § 119(e)(1) Are Satisfied ............... 16
`
`IV.
`
`Joshi ’999 Is Disqualified as Prior Art Under § 103(c)(1) ............................ 17
`
`A.
`
`B.
`
`Joshi ’999 Is Prior Art Only Under § 102(e)....................................... 18
`
`Joshi ’999 and the Claimed Invention Were Commonly Owned
`by or Subject to an Obligation of Assignment to the Same
`Entity When the ’514 Invention Was Made ........................................ 18
`
`1.
`
`2.
`
`Joshi ’999 and the Invention of Claims 1-16 and 20 Were
`Commonly Owned by or Subject to an Obligation of
`Assignment to Fumapharm When Conception Was
`Complete ................................................................................... 19
`
`Joshi ’999 and the Invention of Claims 1-20 Were
`Commonly Owned by or Subject to an Obligation of
`
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`Case No. IPR2015-01993
`Patent 8,399,514
`
`Assignment to Biogen When the Invention Was
`Constructively Reduced to Practice .......................................... 21
`
`V. Kappos 2006 Is Not Prior Art as to Claims 1-16 and 20 ............................... 24
`
`VI. Even If Kappos 2006 and Joshi ’999 Are Prior Art, the ’514 Patent
`Claims Are Not Obvious ............................................................................... 25
`
`A. Kappos 2006 and Joshi ’999 Do Not Disclose a Range of
`Effective Doses Encompassing the Claimed Dose of About 480
`mg/day ................................................................................................. 25
`
`1.
`
`2.
`
`Joshi ’999 Does Not Disclose a Daily Dose ............................. 25
`
`The Phase 2 Study Results of Kappos 2006 Further
`Undermine the Board’s Overlapping Ranges Theory .............. 28
`
`B. One of Ordinary Skill Would Not Have Selected a Dose of
`About 480 mg/day of DMF ................................................................. 29
`
`1.
`
`The ICH Guideline Would Have Provided No Reason to
`Select a Dose of About 480 mg/day ......................................... 29
`
`a.
`
`b.
`
`c.
`
`A Parallel Dose-Response Study Is Necessary to
`Determine a Therapeutically Effective Dose to
`Treat MS ......................................................................... 29
`
`The Study of Kappos 2006 Complied With the
`ICH Guideline ................................................................. 31
`
`The ICH Guideline’s General Guidance on Dose-
`Ranging Studies Fails to Suggest Any Particular
`Dose of DMF to Treat MS .............................................. 33
`
`2.
`
`Gastrointestinal Side Effects Would Have Provided No
`Reason to Select a Dose of About 480 mg/day ........................ 35
`
`C. One of Ordinary Skill Would Not Have Reasonably Expected
`from the Asserted Prior Art that a Dose of About 480 mg/day of
`DMF Would Be Successful ................................................................. 39
`
`ii
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`VII. Objective Evidence Supports Patentability of the ’514 Patent Claims ......... 42
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`Case No. IPR2015-01993
`Patent 8,399,514
`
`
`
`
`A.
`
`B.
`
`C.
`
`The Magnitude of Clinical Efficacy Exhibited by the 480
`mg/day Dose Was Unexpected ........................................................... 43
`Tecfidera® Satisfied a Long-Felt but Unmet Need for a Safe and
`Effective Oral MS Treatment .............................................................. 49
`Tecfidera® Has Been Praised by the Industry ..................................... 53
`
`VIII. Conclusion ..................................................................................................... 54
`
`
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`iii
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`Case No. IPR2015-01993
`Patent 8,399,514
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Federal Cases
`Abbott Labs. v. Sandoz, Inc.,
`544 F.3d 1341 (Fed. Cir. 2008) .......................................................................... 34
`
`Amgen Inc. v. F. Hoffman-La Roche Ltd.,
`580 F.3d 1340 (Fed. Cir. 2009) .......................................................................... 39
`
`Ariad Pharm., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) (en banc) ............................................................ 7
`
`Atofina v. Great Lakes Chem. Corp.,
`441 F.3d 991 (Fed. Cir. 2006) .......................................................... 10, 11, 12, 13
`
`BioGatekeeper, Inc. v. Kyoto Univ.,
`IPR2014-01286, Paper 12 (PTAB Feb. 11, 2015) .............................................. 42
`
`In re Brana,
`51 F.3d 1560 (Fed. Cir. 1995) ............................................................................ 14
`
`Broadcom Corp. v. Emulex Corp.,
`732 F.3d 1325 (Fed. Cir. 2013) .................................................................... 39, 42
`
`ClearValue, Inc. v. Pearl River Polymers, Inc.,
`668 F.3d 1340 (Fed. Cir. 2012) .......................................................................... 12
`
`Corning Inc. v. DSM IP Assets B.V.,
`IPR2013-00053, Paper 66 (PTAB May 1, 2014) ............................. 18, 19, 21, 24
`
`Creative Compounds, LLC v. Starmark Labs.,
`651 F.3d 1303 (Fed. Cir. 2011) .......................................................................... 48
`
`Crocs, Inc. v. Int’l Trade Comm’n,
`598 F.3d 1294 (Fed. Cir. 2010) .......................................................................... 53
`
`iv
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`Page 5 of 65
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`

`

`
`
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) .................................................................... 42, 49
`
`Case No. IPR2015-01993
`Patent 8,399,514
`
`
`
`
`Daiichi Sankyo Co. v. Apotex, Inc.,
`501 F.3d 1254 (Fed. Cir. 2007) ............................................................................ 5
`
`DDB Techs., L.L.C. v. MLB Advanced Media, L.P.,
`517 F.3d 1284 (Fed. Cir. 2008) .............................................................. 19, 21, 22
`
`In re Deuel,
`51 F.3d 1552 (Fed. Cir. 1995) ............................................................................ 34
`
`E.I. du Pont de Nemours & Co. v. MacDermid Printing Sols., L.L.C.,
`525 F.3d 1353 (Fed. Cir. 2008) ............................................................................ 6
`
`Edwards Lifesciences AG v. CoreValve, Inc.,
`699 F.3d 1305 (Fed. Cir. 2012) .......................................................................... 14
`
`In re Glatt Air Techniques, Inc.,
`630 F.3d 1026 (Fed. Cir. 2011) .......................................................................... 53
`
`Ex parte Gleave,
`Appeal No. 2012-009281 (PTAB Jan. 29, 2014) ............................................... 15
`
`Global Tel*Link Corp. v. Securus Techs., Inc.,
`IPR2014-00825, Paper 36 (PTAB Dec. 2, 2015) ......................................... 19, 21
`
`Hybritech Inc. v. Monoclonal Antibodies, Inc.,
`802 F.2d 1367 (Fed. Cir. 1986) .......................................................................... 42
`
`Ineos USA LLC v. Berry Plastics Corp.,
`783 F.3d 865 (Fed. Cir. 2015) ...................................................................... 12, 13
`
`Institut Pasteur & Universite Pierre Et Marie Curie v. Focarino,
`738 F.3d 1337 (Fed. Cir. 2013) .......................................................................... 53
`
`Johnston v. IVAC Corp.,
`885 F.2d 1574 (Fed. Cir. 1989) .......................................................................... 48
`
`v
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`Page 6 of 65
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`

`

`
`
`
`Karsten Mfg. Corp. v. Cleveland Golf Co.,
`242 F.3d 1376 (Fed. Cir. 2001) .......................................................................... 28
`
`Case No. IPR2015-01993
`Patent 8,399,514
`
`
`
`
`Kinetic Techs., Inc. v. Skyworks Sols., Inc.,
`IPR2014-00529, Paper 8 (PTAB Sept. 23, 2014) ............................................... 41
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ............................................................................................ 39
`
`Mintz v. Dietz & Watson, Inc.,
`679 F.3d 1372 (Fed. Cir. 2012) .............................................................. 31, 39, 42
`
`Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc.,
`520 F.3d 1358 (Fed. Cir. 2008) .......................................................................... 39
`
`Procter & Gamble Co. v. Teva Pharm. USA, Inc.,
`566 F.3d 989 (Fed. Cir. 2009) ...................................................................... 47, 49
`
`Purdue Pharma L.P. v. Depomed, Inc.,
`IPR2014-00377, Paper 72 (PTAB July 8, 2015) ................................................ 18
`
`Scott v. Finney,
`34 F.3d 1058 (Fed. Cir. 1994) ............................................................................ 15
`
`In re Soni,
`54 F.3d 746 (Fed. Cir. 1995) ........................................................................ 47, 48
`
`Speedplay, Inc. v. Bebop, Inc.,
`211 F.3d 1245 (Fed. Cir. 2000) .................................................................... 20, 21
`
`Star Sci., Inc. v. R.J. Reynolds Tobacco Co.,
`655 F.3d 1364 (Fed. Cir. 2011) .......................................................................... 34
`
`Titanium Metals Corp.of Am. v. Banner,
`778 F.2d 775 (Fed. Cir. 1985) ............................................................................ 12
`
`TRW Auto. US LLC v. Magna Elecs., Inc.,
`IPR2014-00258, Paper 18 (PTAB Aug. 27, 2014) ............................................. 41
`
`Union Oil Co. of Cal. v. Atl. Richfield Co.,
`208 F.3d 989 (Fed. Cir. 2000) ............................................................................ 13
`
`vi
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`

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`
`
`Vas-Cath Inc. v. Mahurkar,
`935 F.2d 1555 (Fed. Cir. 1991) .................................................................. 7, 8, 13
`
`Case No. IPR2015-01993
`Patent 8,399,514
`
`
`
`
`In re Wertheim,
`541 F.2d 257 (C.C.P.A. 1976) .................................................................... 7, 8, 13
`
`Federal Statutes
`35 U.S.C. § 102 .................................................................................................passim
`
`35 U.S.C. § 103 .................................................................................................passim
`
`35 U.S.C. § 112 .......................................................................................................... 6
`
`35 U.S.C. § 119 .................................................................................................passim
`
`35 U.S.C. § 120 ...................................................................................................... 5, 7
`
`Regulations
`
`37 C.F.R. § 1.41(a)(2) .............................................................................................. 16
`
`37 C.F.R. § 42.24 ....................................................................................................... 6
`
`50 Fed. Reg. 9368-01 (Mar. 7, 1985) ...................................................................... 18
`
`Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,767
`(Aug. 14. 2012) ..................................................................................................... 6
`
`Other Authorities
`
`M.P.E.P. § 706.02(l)(2) ...................................................................................... 18, 19
`
`M.P.E.P. § 2164.02 .................................................................................................. 14
`
`M.P.E.P. § 2164.05 .................................................................................................. 15
`
`Final Rules for Miscellaneous Patent Provisions, 50 Fed. Reg. 9368-
`01 (Mar. 7, 1985) ................................................................................................ 18
`
`
`
`
`
`vii
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`

`

`
`
`
`
`CNS
`
`DMF
`
`Gd+
`
`ICH
`
`MMF
`
`MRI
`
`MS
`
`Nrf2
`
`NQO1
`
`RRMS
`
`FDA
`
`
`
`
`Case No. IPR2015-01993
`Patent 8,399,514
`
`TABLE OF ABBREVIATIONS
`
`Abbreviation
`
`Definition
`
`central nervous system
`
`dimethyl fumarate
`
`gadolinium-enhancing
`
`International Conference on
`Harmonisation
`
`monomethyl fumarate
`
`magnetic resonance imaging
`
`multiple sclerosis
`
`nuclear factor E2-related factor 2
`
`NAD(P)H dehydrogenase, quinone (1)
`
`relapsing-remitting multiple sclerosis
`
`United States Food and Drug
`Administration
`
`
`
`
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`Case No. IPR2015-01993
`Patent 8,399,514
`
`I.
`
`Introduction
`
`Patent owner Biogen MA Inc. respectfully opposes the Petition and the
`
`following grounds of unpatentability that were instituted in this proceeding:
`
`Ground 1: claims 1-6, 8-16, and 20 of the ’514 patent as unpatentable under
`
`§ 103(a) over Kappos 2006, ClinicalTrials, Joshi ʼ999, and ICH Guideline.
`
`Ground 2: claim 7 of the ’514 patent as unpatentable under § 103(a) over
`
`Kappos 2006, ClinicalTrials, Joshi ʼ999, ICH Guideline, and Joshi ʼ992.
`
`Ground 3: claims 17-19 of the ’514 patent as unpatentable under § 103(a)
`
`over Kappos 2006, ClinicalTrials, Joshi ʼ999, ICH Guideline, and Begleiter.
`
`As explained below, because Biogen has met the requirements of 35 U.S.C.
`
`§ 119(e)(1) (pre-AIA), the ’514 patent claims are entitled to the benefit of the
`
`February 8, 2007, filing date of Provisional Application No. 60/888,921. Joshi
`
`’999 is therefore prior art to the ’514 claims only under 35 U.S.C. § 102(e)/103,
`
`and Kappos 2006 is prior art to those claims only under 35 U.S.C. § 102(a)/103.
`
`As prior art only under § 102(e)/103, Joshi ’999 cannot preclude the
`
`patentability of the ’514 patent claims because the subject matter of Joshi ’999 and
`
`the claimed invention were, at the time the claimed invention was made, owned by
`
`or subject to an obligation of assignment to the same entity. 35 U.S.C. § 103(c)(1)
`
`(pre-AIA). Under a September 2003 License Agreement, Joshi ’999 and the
`
`claimed subject matter were owned by or subject to an obligation of assignment to
`
`1
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`Patent 8,399,514
`Fumapharm AG when the invention of the ’514 patent was conceived by February
`
`2004. Biogen subsequently acquired Fumapharm (and all of its assets) in 2006;
`
`thus, Joshi ’999 and the claimed subject matter were owned by or subject to an
`
`obligation of assignment to Biogen when the claimed invention was constructively
`
`reduced to practice in 2007.
`
`Joshi ’999 and the subject matter of the ’514 patent have therefore been
`
`commonly owned by or subject to an obligation of assignment to a single entity at
`
`all relevant times, whether one examines the date of conception (Fumapharm
`
`controlling ownership) or date of constructive reduction to practice (Biogen
`
`controlling ownership). Indeed, they remain commonly owned today (by Biogen).
`
`Accordingly, because all three grounds of unpatentability depend on Joshi ’999,
`
`which is disqualified as prior art under § 103(c)(1), the Board should rule in
`
`Biogen’s favor as to all three grounds and confirm the patentability of claims 1-20.
`
`As the § 103(c)(1) issue is case-dispositive, the Board need not reach any other
`
`issue in this proceeding.
`
`In addition, as established in Biogen’s Motion to Antedate, Dr. Gilmore
`
`O’Neill invented the subject matter of claims 1-16 and 20 before Kappos 2006 was
`
`published. He conceived of the claimed invention by February 2004, and Biogen
`
`was diligent from before the publication of Kappos 2006 until the claimed
`
`invention was constructively reduced to practice on February 8, 2007. As a result,
`
`2
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`Patent 8,399,514
`Kappos 2006 should be removed as prior art to claims 1-16 and 20, and Grounds 1
`
`and 2 are not viable for this independent reason.
`
`Finally, to the extent the Board reaches the merits of the obviousness issues,
`
`which it should not, all three grounds of unpatentability are deficient. The
`
`Institution Decision, for example, states that Joshi ’999 describes a range of 10 to
`
`300 mg of DMF per day to treat MS. But this is simply incorrect. As explained in
`
`the accompanying declaration of Dr. Richard Brundage, Joshi ’999 describes
`
`pharmaceutical preparations containing 10 to 300 mg of DMF, not any particular
`
`daily dose of DMF. The Board’s overlapping ranges theory of obviousness is
`
`therefore based on a fundamental misreading of Joshi ’999.
`
`Further, the Board’s statements regarding the ICH Guideline are also
`
`factually unsupported and contrary to the understanding of persons skilled in the
`
`art. As explained in the accompanying declarations of Dr. Richard Rudick and Dr.
`
`Brundage, for example, dose titration to determine the optimal effective dose for
`
`individual MS patients is not possible and is never performed for an illness such as
`
`MS, which has a long and variable disease course. Rather, clinical trials of disease-
`
`modifying therapy in MS are performed using groups of patients. Nothing in the
`
`ICH Guideline supports the Board’s incorrect assertion that dose titration would be
`
`possible for MS patients or would have led one of ordinary skill to the claimed
`
`therapeutically effective dose of about 480 mg/day of DMF for MS patients.
`
`3
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`The claimed invention also demonstrates significant unexpected results. As
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`explained in the accompanying declarations of Dr. Rudick, Dr. Katherine Dawson,
`
`Dr. Ronald Thisted, and Dr. Brundage, the magnitude of the clinical efficacy
`
`exhibited by the claimed 480 mg/day dose of DMF was surprising, as it proved to
`
`have similar efficacy in MS patients compared to the previously tested 720 mg/day
`
`dose for almost every endpoint measured. One of ordinary skill would not have
`
`expected or predicted this similar efficacy, as Biogen’s expert testimony
`
`establishes.
`
`For these and other reasons detailed below, the Board should confirm the
`
`patentability of the ’514 patent claims.
`
`II.
`
`Petitioner’s Definition of a Person of Ordinary Skill is Overly Broad
`
`Because the ’514 patent claims are directed to a method of treating MS, a
`
`person of ordinary skill in the art should be someone who has at least a medical
`
`degree with at least three years of training in neurology and at least three years of
`
`clinical experience treating MS. (Ex. 2044 ¶ 36.) Dr. Rudick, for example, an MS
`
`clinician with decades of relevant experience, testifies that this definition is
`
`appropriate, and he meets (and exceeds) this level of ordinary skill. (Id.; see also
`
`id. ¶¶ 4-18; Ex. 2045.)
`
`Petitioner, however, proposes that one of ordinary skill would have an
`
`advanced degree in the life sciences and experience with clinical trial design. (Ex.
`
`4
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`1005 ¶ 9.) Thus, according to Petitioner, someone with no MS experience
`
`whatsoever could be one of ordinary skill. (Ex. 2071 at 87:3-7.) Petitioner’s expert
`
`Dr. Steven Linberg, for example, testified that, based on his own understanding of
`
`drug development, he would use the same definition of one of ordinary skill for
`
`patents relating to cardiac drugs, neonatal medications, bronchodilators, and other
`
`medications. (Id. at 87:8-89:21.) But Dr. Linberg has no MS experience or
`
`expertise, and, consequently, his overly broad definition would lead to obviousness
`
`conclusions that one of ordinary skill in the art of treating MS would never reach.
`
`(Ex. 2071 at 24:3-8, 29:7-15, 32:25-33:3, 34:17-35:10, 39:2-18, 40:12-17, 43:12-
`
`14, 44:7-11, 45:2-47:3, 47:7-25, 50:10-12, 50:21-57:7.) The Board should
`
`therefore reject Petitioner’s flawed definition, which disregards the claimed subject
`
`matter. Daiichi Sankyo Co. v. Apotex, Inc., 501 F.3d 1254, 1257 (Fed. Cir. 2007)
`
`(reversing the district court and holding that the person of ordinary skill would be
`
`engaged in developing treatment methods for the ear or a specialist in ear
`
`treatments with training in pharmaceutical formulations and not simply a general
`
`practitioner where the claimed invention related to a method for treating bacterial
`
`ear infections).
`
`III. Biogen Is Entitled to the Filing Date of Its Provisional Application
`A patent application is entitled to the filing date of prior applications as long
`
`as the statutory requirements of §§119(e)(1) and 120 are met. To gain the benefit
`
`5
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`of priority, a provisional application must provide § 112 support for later-claimed
`
`subject matter. 35 U.S.C. § 119(e)(1) (pre-AIA). A non-provisional application
`
`must be filed within twelve months of the provisional application’s filing date and
`
`must have at least one common inventor. Id. Finally, the non-provisional
`
`application must include or be amended to include a specific reference to the
`
`provisional application. Id.; E.I. du Pont de Nemours & Co. v. MacDermid
`
`Printing Sols., L.L.C., 525 F.3d 1353, 1358 (Fed. Cir. 2008).
`
`Despite challenging the ’514 patent in two separate petitions, Petitioner has
`
`never once contested the sufficiency of the provisional application’s disclosure
`
`under § 112. (Pet. at 20; Ex. 2002 at 10-11; see also Paper 17 at 11 (asserting that
`
`lack of priority in first petition was based only on an inventorship issue).) Rather,
`
`Petitioner argues that Kappos 2006 “was previously available as prior art only
`
`under 35 U.S.C. 102(a),” implicitly conceding that the ’514 patent is entitled to its
`
`earliest priority date. (Pet. at 20 (emphasis added).) Petitioner cannot now credibly
`
`maintain the opposite position: that those same claims are not entitled to the benefit
`
`of the provisional application. Further, any attempt by Petitioner to belatedly
`
`support an assertion of lack of priority with expert testimony or other evidence
`
`would constitute improper reply evidence. See 37 C.F.R. § 42.24; Office Patent
`
`Trial Practice Guide, 77 Fed. Reg. 48,756, 48,767 (Aug. 14. 2012).
`
`6
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`Patent 8,399,514
`In any event, for the reasons detailed below, because Biogen’s chain of
`
`applications leading to the ’514 patent meets the requirements of both § 119(e)(1)
`
`and § 120, the ’514 patent claims are entitled to the February 8, 2007, filing date of
`
`U.S. Provisional Application No. 60/888,921 (“the provisional application”).
`
`A. The Provisional Application Provides Written Description
`Support for and Enables the ’514 Patent Claims
`
`As explained by Dr. Daniel Wynn, an MS specialist with nearly thirty years’
`
`experience diagnosing and treating MS patients, the provisional application fully
`
`supports and enables all claims of the ’514 patent. (Ex. 2046 ¶¶ 6-52; Ex. 2047.)
`
`1.
`
`The Provisional Application Provides Written Description
`Support for the ’514 Patent Claims
`
`To meet the written description requirement, a provisional application must
`
`reasonably convey to one of ordinary skill that the inventors possessed the claimed
`
`subject matter. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351–52
`
`(Fed. Cir. 2010) (en banc); In re Wertheim, 541 F.2d 257, 262 (C.C.P.A. 1976).
`
`The provisional application need not describe the claimed subject matter using the
`
`same terms found in the claims, and it may describe more than what is claimed.
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`Wertheim, 541 F.2d at 262-63; see also Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555,
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`1566 (Fed. Cir. 1991) (holding that district court erred by requiring the written
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`description to necessarily exclude all diameters other than those within the claimed
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`range). Written description is a highly factual analysis that must be determined on
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`Case No. IPR2015-01993
`Patent 8,399,514
`a case-by-case basis, and therefore broad, general rules do not apply. Wertheim,
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`541 F.2d at 262-63; Vas-Cath, 935 F.2d at 1562 (the precedential value of cases in
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`this area is extremely limited).
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`Here, the provisional application shows that the inventors possessed the
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`claimed invention. (Ex. 2046 ¶¶ 27-45, Appendix A.) Independent claims 1, 11,
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`15, and 20 define methods of treating MS by administering about 480 mg per day
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`of DMF, MMF, or a combination thereof. (Ex. 2046 ¶ 5; Ex. 1001 at 27:59-67,
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`29:19-22, 30:1-7, 30:22-28.) Claims 6 and 12 specify DMF, while claim 7 provides
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`for administering MMF. (Ex. 2046 ¶ 5; Ex. 1001 at 29:4-9, 29:23-24.) Claim 2
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`specifies the form of the pharmaceutical composition. (Ex. 2046 ¶ 5; Ex. 1001 at
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`28:58-60.) Claims 3-5, 9, 13, 14, and 16 specify frequency of administration. (Ex.
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`2046 ¶ 5; Ex. 1001 at 28:61-29:3, 29:13-15, 29:25-28, 30:8-9.) Claims 8 and 10
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`provide that the therapeutically effective dose is administered to the subject for at
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`least 12 weeks. (Ex. 2046 ¶ 5; Ex. 1001 at 29:10-12, 29:16-18.) And claims 17-19
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`depend from claims 1, 11, and 15, respectively, and specify that the expression
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`level of NQO1 is elevated after administering DMF, MMF, or a combination
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`thereof. (Ex. 2046 ¶ 5; Ex. 1001 at 30:10-21.)
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`The provisional application fully supports these claims. (Ex. 2046 ¶¶ 28-45,
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`Appendix A.) It singles out MS as a chronic, progressive, and severely disabling
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`neurological disease. (Ex. 2046 ¶¶ 29-31; Ex. 1012 ¶¶ [0001]-[0004].) The
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`inventors describe methods
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`for
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`Case No. IPR2015-01993
`Patent 8,399,514
`screening, evaluating, and comparing
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`neuroprotective properties of compounds based on Nrf2 pathway upregulation with
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`the specific goal of treating MS. (Ex. 2046 ¶¶ 32-34; Ex. 1012 ¶¶ [0010], [0011],
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`[0020], [0021], [0041]-[0062], [0063], [0065]-[0067].) In fact, the provisional
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`application describes methods of treating neurological diseases, including MS.
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`(Ex. 2046 ¶ 33-34; see also Ex. 1012 ¶¶ [0010], [0011], [0020], [0021], [0063],
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`[0065]-[0067].) It describes a dose of DMF or MMF of “about 480 mg” per day as
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`therapeutically effective for such treatment methods. (Ex. 2046 ¶¶ 35-38; Ex. 1012
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`¶ [0116].)
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`In particular, the provisional application identifies “about 480 mg per day”
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`of DMF or MMF as the lower endpoint of a preferred dose range: from about 480
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`mg to about 720 mg per day. (Ex. 2046 ¶¶ 37-38; Ex. 1012 ¶ [0116].) Because a
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`person of ordinary skill would have understood that DMF and MMF would be
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`administered as a specific daily dose—and not a range of doses—the provisional
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`application describes a discrete dose of “about 480 mg per day” of DMF or MMF.
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`(Ex. 2046 ¶¶ 36, 38.) In fact, it directs the skilled artisan to about 480 mg/day by
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`describing a series of progressively narrower dose ranges, i.e., from about 240 mg
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`to about 720 mg/day, from about 480 mg to about 720 mg/day, and about 720
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`mg/day. (Ex. 2046 ¶¶ 37-38; Ex. 1012 ¶ [0116].) The range is narrowed by raising
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`the lower endpoint and maintaining the same upper endpoint of about 720 mg/day.
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`Case No. IPR2015-01993
`Patent 8,399,514
`(Ex. 2046 ¶¶ 37-38.) As such, the provisional application singles out and describes
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`the preferred, discrete dose of about 480 mg/day as a therapeutically effective dose
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`of DMF or MMF. (Ex. 2046 ¶¶ 37-38; Ex. 1012 ¶ [0116].)
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`The provisional application also states that the pharmaceutical compositions
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`used to treat MS contain excipients and that administration may be oral or by other
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`routes. (Ex. 2046 ¶¶ 39-41; Ex. 1012 ¶¶ [0118]-[0110].) It also indicates that DMF
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`may be administered in separate doses, such as 2, 3, 4, or 6 equal doses. (Ex. 2046
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`¶ 42; Ex. 1012 ¶¶ [0116], [0120].) Consistent with the chronic nature of MS, the
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`provisional application also describes treating an MS patient with DMF or MMF
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`for a long period of time, e.g., for at least 12 weeks. (Ex. 1012 ¶ [0067].) Based on
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`these express disclosures, a person of ordinary skill would have readily understood
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`that the inventors possessed the claimed subject matter when the provisional
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`application was filed. (Ex. 2046 ¶¶ 43-45, 59.)
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`Atofina Does Not Affect Biogen’s Entitlement to Priority
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`2.
`In its Institution Decision, the Board asked Biogen to address why it should
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`be accorded benefit of the provisional application in light of Atofina v. Great Lakes
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`Chem. Corp., 441 F.3d 991 (Fed. Cir. 2006). (Paper 20 at 9.) For the reasons
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`explained below, Atofina’s endpoint language is wholly inapplicable to written
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`description and does not control here.
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`Case No. IPR2015-01993
`Patent 8,399,514
`Atofina Applies Only Within the Limited Context of
`Anticipation
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`a.
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`Citing Atofina, the Board stated that “the disclosure of a range is not a
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`disclosure of end points of the range any more than it is of each of the intermediate
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`points.” (Paper 20 at 8-9.) The Board then noted that since about 480 mg/day is an
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`endpoint, Biogen should address why it is entitled to its provisional filing date in
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`light of Atofina. (Paper 20 at 9.) Atofina, however, including its endpoint language,
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`applies only to factually analogous cases within the limited context of prior-art
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`anticipation. It serves a specific purpose—to prevent broad prior-art ranges from
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`necessarily anticipating claimed ranges no matter how slight the overlap. It does
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`not establish a sweeping rule meant to deprive written description support for
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`claim terms expressly identified in a patent’s specification. No judicial decision
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`supports such a broad reading of Atofina.
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`In Atofina, the claims recited a temperature range of 330-450 °C. Atofina,
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`441 F.3d at 999. The prior art disclosed a much broader range (100-500 °C) and a
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`preferred range of 150-350 °C. Id. The Court determined that no reasonable
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`factfinder could conclude that the broad (100-500 °C) range anticipated the
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`narrower claimed range. Id. In addition, because the claimed range only slightly
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`overlapped with the preferred prior-art range, and evidence showed that the
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`claimed range was critical, the Court reversed the district court’s anticipation
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`Case No. IPR2015-01993
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`finding. Id. at 999-1000; see also ClearValue, Inc. v. Pearl River Polymers, Inc.,
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`668 F.3d 1340, 1345 (Fed. Cir. 2012).
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`The Federal Circuit clarified its Atofina holding in ClearValue, stating that
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`the considerable difference between the claimed and prior-art temperature ranges
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`precluded a finding of anticipation. ClearValue, 668 F.3d at 1345. Further, as
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`explained in ClearValue and Ineos, whether a prior-art range anticipates a claimed
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`range depends on whether the claimed range is critical to the invention’s
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`operability as compared to the prior-art disclosure. See Ineos USA LLC v. Berry
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`Plastics Corp., 783 F.3d 865, 869 (Fed. Cir. 2015) (“In Atofina, we reversed the
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`district court’s finding of anticipation where the patent-in-suit claimed a
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`temperature range that was critical to the operability of the invention and the range
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`disclosed in the prior art was substantially different.”); ClearValue, 668 F.3d at
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`1345 (the claimed temperature range in Atofina was critical to enable the process to
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`operate effectively)