Case IPR2016-01490
`Patent No. 8,637,553
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`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`FUSTIBAL LLC,
`Petitioner,
`
`v.
`
`BAYER HEALTHCARE LLC,
`Patent Owner.
`__________________
`
`Case No: IPR2016-01490
`Patent No. 8,637,553
`__________________
`
`PATENT OWNER PRELIMINARY RESPONSE
`
`
`
`

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`
`
`TABLE OF CONTENTS
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`Case IPR2016-01490
`Patent No. 8,637,553
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`INTRODUCTION ........................................................................................... 1 
`I. 
`BACKGROUND ON REGORAFENIB ......................................................... 4 
`II. 
`III.  THE PERSON OF ORDINARY SKILL IN THE ART ................................. 6 
`IV.  CLAIM CONSTRUCTION ............................................................................ 6 
`ARGUMENT ............................................................................................................. 7 
`TRIAL SHOULD NOT BE INSTITUTED ON GROUND 1
`I. 
`(ANTICIPATION) FOR ANY CLAIM OF THE ’553 PATENT. ................. 7 
`A.  Ground 1 Should Not Be Instituted Pursuant to Section 325(d). .......... 7 
`The Petition Does Not Establish a Reasonable Likelihood that
`B. 
`the Petitioner Would Prevail on Its Anticipation Challenge to
`Claim 13. ............................................................................................... 8 
`1. 
`Riedl Does Not Anticipate As a Matter of Law. ........................ 9 
`2. 
`The Petition Reflects that Its Arguments Are Premised on
`Obviousness, Not Anticipation. ................................................ 17 
`The Petition’s Anticipation Arguments Are Unsupported
`by Evidence. .............................................................................. 19 
`The Petition Does Not Establish a Reasonable Likelihood that
`the Petitioner Would Prevail on Its Anticipation Challenge to
`the Remaining Claims. ........................................................................ 20 
`TRIAL SHOULD NOT BE INSTITUTED ON ANY OF GROUNDS
`2–5 (OBVIOUSNESS) FOR ANY CLAIM OF THE ’553 PATENT. ......... 21 
`A.  Grounds 2–5 Suffer from Several Flaws that Render Them
`Deficient as a Matter of Law. .............................................................. 22 
`The Petition Fails to Perform Any Lead Compound
`1. 
`Analysis. .................................................................................... 22 
`
`3. 
`
`C. 
`
`II. 
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`2. 
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`Case IPR2016-01490
`Patent No. 8,637,553
`The Logic of the Petition’s Obviousness Analysis is
`Flawed and Inconsistent. ........................................................... 25 
`Grounds 2–5 Are Unsupported by Evidence Concerning
`the Understanding of the POSA ................................................ 33 
`The Legal Authority Cited in the Petition Does Not
`Support Instituting Trial ............................................................ 34 
`B.  Ground 2 Fails Because Riedl Has Already Been Considered by
`the Office. ............................................................................................ 36 
`
`3. 
`
`4. 
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`Case IPR2016-01490
`Patent No. 8,637,553
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`
`
`TABLE OF AUTHORITIES
`
`FEDERAL CASES
`Atofina v. Great Lakes Chem. Corp., 441 F.3d 991 (Fed. Cir. 2006) ............... 10, 11
`
`Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293
`(Fed. Cir. 2007) ................................................................................................... 34
`
`Bristol-Myers Squibb Co. v. Teva Pharm. USA, Inc., 752 F.3d 967
`(Fed. Cir. 2014) ............................................................................................. 23, 26
`
`Callaway Golf Co. v. Acushnet Co., 576 F.3d 1331 (Fed. Cir. 2009) ..................... 18
`
`Daiichi Sankyo Co. v. Matrix Labs., 619 F.3d 1346 (Fed. Cir. 2010) ......... 23, 25, 30
`
`Eisai Co. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353 (Fed. Cir. 2008) .............. 26, 27
`
`Eli Lilly & Co. v. Bd. of Regents of Univ. of Wash., 334 F.3d 1264
`(Fed. Cir. 2003) ................................................................................................... 10
`
`Eli Lilly & Co. v. Zenith Goldline Pharm., Inc., No. IP 99-38-C H/K,
`2001 WL 1397304 (S.D. Ind. Oct. 29, 2001) ..................................................... 26
`
`Impax Labs. v. Aventis Pharm. Inc., 468 F.3d 1366 (Fed. Cir. 2006) ......... 10, 11, 15
`
`In re Armodafinil Patent Litig. Inc., 939 F. Supp. 2d 456 (D. Del.
`2013) ................................................................................................................... 36
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012) .................................................... 31
`
`In re Petering, 301 F.2d 676 (C.C.P.A. 1962) ................................................... 10, 11
`
`In re Ruschig, 343 F.2d 965 (C.C.P.A. 1965).......................................................... 11
`
`Institut Pasteur & Universite Pierre et Marie Curie v. Focarino, 738
`F.3d 1337 (Fed. Cir. 2013) ................................................................................. 25
`
`KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) ................................................ 26
`
`Leo Pharm. Prods. v. Rea, 726 F.3d 1346 (Fed. Cir. 2013) .................................... 26
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`Case IPR2016-01490
`Patent No. 8,637,553
`Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359 (Fed. Cir. 2008) ............... 16, 18
`
`Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358 (Fed.
`Cir. 2008) ............................................................................................................ 27
`
`Otsuka Pharm. v. Sandoz, Inc., 678 F.3d 1280 (Fed. Cir. 2012) ......................passim
`
`Perricone v. Medicis Pharmaceutical Corp., 432 F.3d 1368 (Fed. Cir.
`2005) ............................................................................................................. 16, 17
`
`Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007) .................................... 35
`
`Pfizer Inc. v. Mylan Pharm. Inc., 71 F. Supp. 3d 458, 468–69 (D. Del.
`2014), aff’d per curiam, 628 F. App’x 764 (Fed. Cir. 2016) ............................. 36
`
`Pfizer Inc. v. Teva Pharm. USA, Inc., 555 F. App’x 961 (Fed. Cir.
`2014) ................................................................................................................... 25
`
`Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989 (Fed.
`Cir. 2009) ................................................................................................ 22, 24, 26
`
`Takeda Chem. Indus. v. Alphapharm Pty., 492 F.3d 1350 (Fed. Cir.
`2007) ............................................................................................................passim
`
`Takeda Pharm. Co. v. Handa Pharm., LLC, Nos. C-11-00840 JCS et
`al., 2013 WL 9853725 (N.D. Cal. Oct. 17, 2013) .............................................. 36
`
`Taltech Ltd. v. Esquel Enters., 604 F.3d 1324 (Fed. Cir. 2010) .............................. 11
`
`Vanda Pharm. Inc. v. Roxane Labs., Inc., Nos. CV 13-1973-GMS, 14-
`757-GMS, 2016 WL 4490701 (D. Del. Aug. 25, 2016) ..................................... 31
`
`Vizio, Inc. v. Int’l Trade Comm’n, 605 F.3d 1330 (Fed. Cir. 2010) .................. 16, 18
`
`Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc., 231 F.3d 1339
`(Fed. Cir. 2000) ................................................................................................... 23
`
`OTHER AUTHORITIES
`
`37 C.F.R. § 42.2 ................................................................................................. 19, 33
`
`37 C.F.R. § 42.63 ..................................................................................................... 19
`
`28 U.S.C. § 1746 ................................................................................................ 20, 33
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`35 U.S.C. § 325 .................................................................................................... 7, 36
`
`Bumble Bee Foods, LLC v. Kowalski, IPR2014-00224 (P.T.A.B. June
`5, 2014) ......................................................................................................... 20, 33
`
`FedEx Corp. v. Ronald A. Katz Tech. Licensing, CBM2015-00053
`(P.T.A.B. June 29, 2015) .............................................................................. 20, 33
`
`Hosp. Core Servs. LLC v. Nomadix, Inc., IPR2016-00052, 2016 WL
`2909164 (P.T.A.B. Apr. 27, 2016) ....................................................................... 7
`
`Nora Lighting, Inc. v. Juno Mfg., IPR2015-00601, 2015 WL 5029349
`(P.T.A.B. Aug. 12, 2015) ...................................................................................... 7
`
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`Case IPR2016-01490
`Patent No. 8,637,553
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`I.
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`INTRODUCTION
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`This proceeding involves a challenge to the patentability of the chemical
`
`compound regorafenib. Regorafenib is the active ingredient in the FDA-approved
`
`anti-cancer therapy STIVARGA®, a product that has helped many thousands of
`
`patients over the last four years. STIVARGA® is indicated for certain types of
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`colorectal cancer, one of the most common types of cancer in the world. See Ex.
`
`2001 at 1. It is also approved to treat gastrointestinal stromal tumors (GIST) and
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`has received orphan drug exclusivity for this indication. Id.; Ex. 2003 at 1.
`
`Patent Owner Bayer HealthCare LLC’s (“Bayer”) position is that, as of the
`
`relevant date, regorafenib was a novel compound, and that the prior art and
`
`objective evidence of nonobviousness support its patentability. Bayer stands
`
`prepared to offer evidence in support of this position if necessary. However, it is
`
`respectfully submitted that Bayer need not do so, as the Petition is deficient on its
`
`face and fails to establish a reasonable likelihood that Petitioner Fustibal would
`
`prevail in showing that any challenged claim of U.S. Patent No. 8,637,553 (the
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`“’553 patent”) is unpatentable.
`
`Ground 1 of the Petition asserts that all claims of the ’553 patent are
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`anticipated by Riedl (Ex. 1002). That is wrong, evidenced best by the fact that
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`Riedl was analyzed extensively by the Examiner during prosecution and deemed
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`not to be novelty-destroying. That alone is a reason for the Board to deny
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`institution. But even on the substance, Ground 1 fails. There is no dispute that
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`Riedl and the challenged claims stand in a genus-species relationship, or that the
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`general rule is that the disclosure of a genus does not anticipate an individual
`
`species within the genus. It is true, as the Petition notes, that there is a narrow
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`exception to this rule which holds that a genus can anticipate a species, but only
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`where the genus is so small that the person of ordinary skill in the art (the
`
`“POSA”) would at once recognize every species within the genus. That rule,
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`however, has no applicability here. While Formula I of Riedl—which the Petition
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`relies upon in part—does cover regorafenib, that genus is immense. In recognition
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`of this fatal flaw, the Petition proceeds to create a new “genus” of compounds that
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`does not actually exist in Riedl, and then declares that genus to be small enough to
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`anticipate regorafenib. That is legally impermissible—the Petition cannot re-write
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`a prior art reference in order to present an invalidity challenge.
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`Indeed, what the Petition really seeks to do with Ground 1 is to run an
`
`obviousness argument under the guise of an anticipation argument. This is evident
`
`from the Petition itself, which is framed in terms of what would be “apparent to
`
`one of skill in the art who was looking to modify sorafenib.” Pet. at 16 (emphasis
`
`added). The issue of whether the POSA was “looking to modify” a prior art
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`disclosure, however, is a classic obviousness argument under 35 U.S.C. § 103, not
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`an anticipation argument under 35 U.S.C. § 102. The Petition’s anticipation
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`position thus is deficient as a matter of law.
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`The Petition’s obviousness arguments fare no better, as they all suffer from
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`multiple flaws that render them legally and factual deficient.
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`First, this is a chemical compound case, and as such the required first step in
`
`any obviousness inquiry is an analysis of the selection of a “lead compound” by
`
`the POSA. But the Petition nowhere engages in this analysis. Instead, the Petition
`
`assumes that the POSA would start with sorafenib and modify it. See, e.g., Pet. at
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`5–6. That is wholly impermissible. A party challenging the obviousness of a
`
`chemical compound must explain why the POSA would select the particular lead
`
`compound at issue over other compounds in the art. See, e.g., Otsuka Pharm. v.
`
`Sandoz, Inc., 678 F.3d 1280, 1291–92 (Fed. Cir. 2012). Without such analysis, the
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`Petition’s obviousness Grounds are deficient as a matter of law.
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`Second, the Petition’s obviousness arguments are premised on the notion
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`that, of all the potential modifications one could make, the POSA somehow would
`
`have a reason to (1) add one—and only one—fluorine atom to sorafenib at a
`
`specific position on the molecule, and (2) make no other modifications. The
`
`arguments in the Petition, however, contain a series of critical gaps and
`
`inconsistencies. For example, while the Petition touts the benefits of “introduction
`
`of fluorine into drugs,” see, e.g., Pet. at 27, 41, 49, it entirely overlooks that
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`sorafenib is already fluorinated with three fluorine atoms, i.e., it has a
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`trifluoromethyl group. The Petition presents no explanation as to why the POSA
`
`would take an already multi-fluorinated molecule and fluorinate it further.
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`Similarly, the Petition asserts that fluorination has manifold benefits, in particular
`
`increasing lipophilicity, blocking metabolism, and improving efficacy. However,
`
`even assuming the Petition is correct that fluorination can be beneficial, it is
`
`indisputable that fluorination is not always beneficial—otherwise, every marketed
`
`pharmaceutical would contain a fluorine atom, which is plainly not the case. And
`
`on that topic, the Petition fails to provide evidence or analysis as to why the POSA
`
`would expect fluorination on the central phenyl ring to be beneficial in this
`
`particular case given what was known about the properties of sorafenib.
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`In sum, none of the Grounds in the Petition establishes a reasonable
`
`likelihood that any claim of the ’553 patent is unpatentable. Trial should not be
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`instituted.
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`II. BACKGROUND ON REGORAFENIB
`Protein kinases regulate cellular activity—in particular, pathways that lead
`
`to cellular responses such as growth and division. Some years ago, scientists
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`began to appreciate the critical role of abnormal protein kinase activity in a range
`
`of disorders, including cancer. It was thought that inhibiting specific kinase
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`activity might in turn inhibit tumor formation and growth. As such, researchers
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`began investigating potential protein kinase inhibitors and evaluating their efficacy
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`as anti-cancer compounds.
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`One compound that arose from these efforts is regorafenib. Regorafenib,
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`which has the chemical structure depicted below, is an inhibitor of multiple
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`kinases:
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`
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`Regorafenib is the active ingredient in Bayer’s highly successful cancer drug
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`STIVARGA® and is covered by various claims of the ’553 patent.
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`Regorafenib was not the first potent kinase inhibitor discovered in Bayer’s
`
`laboratories. In the 1990s, after years of research, Bayer scientists synthesized the
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`compound sorafenib, a kinase inhibitor with the structure below:
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`Bayer subsequently applied for and obtained several patents relating to sorafenib,
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`including patents directed to the compound itself and methods of using it. Riedl is
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`the PCT publication of one of those applications. The tosylate salt of sorafenib is
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`the active ingredient in the drug product NEXAVAR®, which FDA first approved
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`as a cancer therapy in December 2005. NEXAVAR® is indicated for the treatment
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`of certain types of liver cancer, kidney cancer, and thyroid cancer. Ex. 2004 at 1.
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`Following the discovery of sorafenib, Bayer scientists commenced work on
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`a second-generation kinase inhibitor. It was during this research that Bayer
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`scientists discovered regorafenib. Regorafenib was ultimately selected by Bayer
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`for clinical development and received its first FDA approval as a cancer therapy in
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`November 2012.
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`III. THE PERSON OF ORDINARY SKILL IN THE ART
`For purposes of this preliminary response only, Bayer does not challenge the
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`Petition’s proposed definition of the POSA.1 See Pet. at 6.
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`IV. CLAIM CONSTRUCTION
`For purposes of this preliminary response only, Bayer does not challenge the
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`claim constructions proposed in the Petition.2 See id. at 6–7.
`
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`1 In the event that the Board institutes trial, Bayer reserves the right to offer a
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`different definition of the POSA.
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`2 In the event that the Board institutes trial, Bayer reserves the right to propose
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`different claim constructions.
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`ARGUMENT
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`I.
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`TRIAL SHOULD NOT BE INSTITUTED ON GROUND 1
`(ANTICIPATION) FOR ANY CLAIM OF THE ’553 PATENT.
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`For Ground 1 of the Petition, the Petition asserts that all of the claims of the
`
`’553 patent are anticipated by Riedl (Ex. 1002), a PCT publication that discloses
`
`the chemical structure of sorafenib. However, as discussed further below, not only
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`should the Board exercise its discretion under Section 325(d) and decline to
`
`institute trial based on Ground 1, but the Board should reject Ground 1 because it
`
`fails to show anticipation as a matter of law.
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`A. Ground 1 Should Not Be Instituted Pursuant to Section 325(d).
`As an initial matter, the Board should deny Ground 1 of the Petition because
`
`the Office has already fully considered the patentability of the claims of the ’553
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`patent in view of Riedl. Section 325(d) of Title 35 provides that, during an inter
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`partes review, the Board “may take into account whether, and reject the petition or
`
`request because, the same or substantially the same prior art or arguments
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`previously were presented to the Office.” 35 U.S.C. § 325(d); see also Hosp. Core
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`Servs. LLC v. Nomadix, Inc., IPR2016-00052, 2016 WL 2909164, at *6–8
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`(P.T.A.B. Apr. 27, 2016) (Paper 8) (declining to institute inter partes review “in
`
`view of [the Board’s] discretion under 35 U.S.C. § 325(d)”); Nora Lighting, Inc. v.
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`Juno Mfg., IPR2015-00601, 2015 WL 5029349, at *5–6 (P.T.A.B. Aug. 12, 2015)
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`(Paper 13) (same).
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`Here, Riedl was expressly considered by the Examiner during prosecution of
`
`the ’553 patent. See, e.g., Ex. 1001 at 5 (listing WO 00/42012 as Foreign Patent
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`Document considered); id. at col. 8, ll. 60–61 (identifying Riedl). Indeed, in
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`allowing the ’553 patent to issue, the Examiner referred to Riedl specifically and—
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`on multiple occasions—rejected the notion that it rendered regorafenib
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`unpatentable, stating that the publication “fails to teach or render obvious the
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`instant claimed compounds . . . and does not fairly suggest their salts or
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`pharmaceutical compositions.” Ex. 2006 at 912–13 (emphases added).3 The
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`Board should therefore exercise its discretion under Section 325(d) to deny any
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`ground of the Petition that is based solely on Riedl, including Ground 1 (and
`
`Ground 2, discussed further below).
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`B.
`
`The Petition Does Not Establish a Reasonable Likelihood that the
`Petitioner Would Prevail on Its Anticipation Challenge to Claim
`13.
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`Claim 13 of the ’553 patent requires a compound with the chemical structure
`
`of regorafenib. Ex. 1001 at col. 40, ll. 4–16. The Petition argues that Riedl
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`“expressly discloses the regorafenib compound, rendering claim 13 anticipated.”
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`3 See also Ex. 2005 at 352–53, 397; Ex. 2006 at 569, 645–46, 670–71, 854–55,
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`901–02.
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`Pet. at 16. For multiple reasons, however, the Petition’s arguments are legally
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`insufficient to establish anticipation.
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`Riedl Does Not Anticipate As a Matter of Law.
`
`1.
`The Petition’s genus-species anticipation argument is deficient as a matter of
`
`law because it improperly relies on an artificial genus found nowhere in Riedl. See
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`Pet. at 15. In other words, while Riedl does disclose genera that encompass
`
`regorafenib, the Petition does not actually rely on any of those genera, but instead
`
`concocts a new genus that does not exist in Riedl.
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`As the Examiner recognized during prosecution, Riedl does not expressly
`
`disclose regorafenib. See, e.g., Ex. 2006 at 912–13. It neither identifies its
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`chemical name nor provides a drawing of its chemical structure. Rather, Riedl
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`discloses a broad genus (Formula I) that covers a vast array of compounds,
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`including regorafenib. See Ex. 1002 at 2–6. A number of the generic claims,
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`including claim 1, likewise encompass regorafenib. See, e.g., id. at 89–91.
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`Similarly, in the litigation against Onyx that is referenced in the Petition, Pet. at 10,
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`Bayer took the position that U.S. Patent No. 7,351,834 (which is related to Riedl)
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`contains generic claims that cover regorafenib, see Ex. 1003 at 15.4
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`The law is well established that “the disclosure of a genus in the prior art is
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`not necessarily a disclosure of every species that is a member of that genus.”
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`Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 999 (Fed. Cir. 2006); see also
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`Eli Lilly & Co. v. Bd. of Regents of Univ. of Wash., 334 F.3d 1264, 1270 (Fed. Cir.
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`2003) (noting that “earlier disclosure of a genus does not necessarily prevent
`
`patenting a species member of the genus”). Rather, only when the prior art genus
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`is so limited in number and so well-defined that the POSA “should be able to ‘at
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`once envisage each member of th[e] . . . class’” can the reference disclosing the
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`genus be found to anticipate an individual species falling within that class. Impax
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`Labs. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383 (Fed. Cir. 2006) (quoting In re
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`Petering, 301 F.2d 676, 681 (C.C.P.A. 1962)) (affirming district court’s finding
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`that reference did not anticipate where a “large number of compounds [were]
`
`included in formula I” and the reference contained “no specific identification of
`
`[the compound claimed by the patent-in-suit]”). Thus, a narrow genus that
`
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`4 For clarity, the litigation between Bayer and Onyx was a contract dispute, not a
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`patent infringement action. It did not involve an adjudication of the scope or
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`validity of the ’553 patent.
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`contains only a small number of species may anticipate each of those species it
`
`encompasses, see, e.g., In re Petering, 301 F.2d at 681 (“only 20 compounds”); see
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`also Atofina, 441 F.3d at 999 (“[A] a very small genus can be a disclosure of each
`
`species within the genus.”), while a broader genus will not anticipate each of the
`
`large number of species it includes, see, e.g., Taltech Ltd. v. Esquel Enters., 604
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`F.3d 1324, 1332 (Fed. Cir. 2010) (“hundred[s] of materials and resins”); Impax
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`Labs., 468 F.3d at 1383 (“hundreds of compounds included in formula I”); Atofina,
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`441 F.3d at 999 (“[a] temperature range of over 100 degrees”); In re Ruschig, 343
`
`F.2d 965, 974 (C.C.P.A. 1965) (references describing genera of 130 and 156
`
`compounds).
`
`As a matter of law, the genera in Riedl that encompass regorafenib are too
`
`large to anticipate an individual species like regorafenib. For example, Formula I
`
`has the structure A – D – B, where the “D” urea remains constant but both the “A”
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`and “B” portions of the molecule are complex variables. See Ex. 1002 at 2–6.
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`Over more than three pages of the application, Riedl sets forth the many options
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`and substitutions permitted for the A and B moieties. Id. at 3–6. “A” actually
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`represents yet another formula (“-L-(M-L1)q”) that is “a substituted moiety of up to
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`40 carbon atoms.” Id. at 3. Similarly, “B” is “a substituted or unsubstituted, up to
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`tricyclic aryl or heteroaryl moiety of up to 30 carbon atoms with a least one 6-
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`member cyclic structure bound directly to D containing 0‒4 members of the group
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`consisting of nitrogen, oxygen, and sulfur.” Id. All told, Formula I encompasses
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`well in excess of a billion compounds.
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`This extensive breadth of Formula I is reflected in the prosecution history
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`for U.S. Application No. 09/889,227, which is a Section 371 of the International
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`Application (PCT/US00/00648) that published as Riedl. Specifically, in an office
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`action requiring restriction under 35 U.S.C. §§ 121 and 372, the Examiner issued a
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`fifteen-way restriction requirement in light of the fact that various generic claims
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`that were based on Formula I contained a wide and disparate array of variables.
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`The Examiner stated:
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`The different A, B with the L, L1, M’s and the various hetero rings and
`substituents have so many variables with the heterocyclic and non-
`hetero groupings, they have different bonding and properties, and have
`achieved a different status in the art, and is burdensome to search and
`hence are objected to on the grounds that they lack a common nucleus.
`The terms A, L, L1, M, and the various het groups and rings, are so
`broad in scope that a prior art reference anticipating the claims with
`respect to one member under 35 USC 102(b) would not render obvious
`the same claims under 35 USC 103a with respect to another member.
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`Ex. 2007 at 282–84. None of the groups set forth in the restriction requirement
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`corresponds to the “genus” relied upon in the Petition.
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`In apparent recognition of these facts, the Petition does not rely upon
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`Formula I itself or any other genus that is actually in Riedl to argue anticipation.
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`Instead, the Petition constructs a novel “genus” that does not exist in Riedl and
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`then seeks to rely on that phantom “genus” to argue anticipation. Specifically,
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`rather than referring to a Markush group or other pre-existing group of compounds,
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`the Petition does the following:
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`
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`First, the Petition turns to an example in Riedl disclosing the structure
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`of and a method for the synthesis of sorafenib. Pet. at 8 (citing Ex.
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`1002 at 42);
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`
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`Then, the Petition turns to another example in Riedl and observes that
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`it discloses a method of synthesis for a compound structurally
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`identical to sorafenib, except that it contains a methyl substituent in
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`the 3-position. Id. at 14 (citing Ex. 1002 at 43);
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`
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`The Petition then turns to the Syntheses of Exemplified Compounds
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`(“Examples”), which run from pages 53 to 75 of Riedl, and the Tables
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`of individual examples, which run from pages 76 to 88 of Riedl and
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`depict compounds identified in the Examples. The Examples and the
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`Tables set forth 103 individual compounds, not a defined genus of
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`compounds; indeed, the Petition nowhere argues that they comprise a
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`genus. Nor does the Petition argue that either the Examples or the
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`Tables encompass regorafenib (and, in fact, they do not);
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`Rather, the Petition extracts from these Examples/Tables another
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`
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`individual compound (entry 49), noting that it is structurally identical
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`to sorafenib, except that it is chloro-substituted in the 3′-position. Id.
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`at 14. The Petition further asserts that such a compound is the same
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`as sorafenib being substituted by chlorine in the 3-position. Id.;
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`
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`After that, the Petition skips ahead to another individual compound
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`(entry 52) in the Examples/Tables, noting that it is structurally
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`identical to sorafenib, except that it is chloro-substituted in the 2′-
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`position. Id. The Petition asserts that such a compound is the same as
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`sorafenib being substituted by chlorine in the 2-position. Id.;
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`
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`Still not having identified an actual genus in Riedl or any disclosure of
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`regorafenib—and in apparent recognition that none of the 103
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`compounds in the Examples or Tables of Riedl discloses a compound
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`with a fluoro substituent anywhere on the central ring bound to the
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`urea (variable “D”), let alone regorafenib—the Petition then swings
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`all the way back to Formula I, which begins dozens of pages earlier on
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`page 2. Id.;
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`
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`As noted above, Formula I spans multiple pages and encompasses a
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`wide variety of variables. Ex. 1002 at 2–6. Nevertheless, the Petition
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`selectively plucks out the final paragraph of Formula I, which states,
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`“Suitable halogen groups include F, Cl, Br, and/or I, from one to per-
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`substitution (i.e., all H atoms on a group replaced by a halogen atom)
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`being possible where an alkyl group is substituted by halogen, mixed
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`substitution of halogen atom types also being possible on a given
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`moiety.” Pet. at 9 (quoting Ex. 1002 at 6);
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`
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`Finally, the Petition pulls together these disparate disclosures, and
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`asserts that it constitutes a “genus” of “eight individual chemical
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`compounds possible when substituting a halogen (of one of the
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`suitable halogen groups disclosed by Riedl [(F, Cl, Br, or I)] at one of
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`these positions [(positions 3/3′ and 2/2′)].” Id. at 16. The Petition
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`then argues that “[t]hese eight possible compounds are disclosed and
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`would be readily apparent to one of skill in the art who was looking to
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`modify sorafenib.” Id.
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`What the Petition has done is antithetical to the law of anticipation. The law
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`does not permit the Petition to selectively pick and choose disparate aspects of a
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`disclosure, sew them together into a new genus of chemical compounds, and then
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`argue that this new genus is anticipatory. Rather, the case law focuses on whether,
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`based on a genus of compounds that is actually in the reference, the genus is so
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`small that the POSA would be able to envision its individual members. See, e.g.,
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`Impax Labs., 468 F.3d at 1383. Indeed, if the Petition’s approach were correct,
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`any reference that disclosed all of the individual components of a molecule—no
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`matter where they were in a reference, and irrespective of whether or not they were
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`grouped together—would be anticipatory, because one could, using hindsight,
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`select the correct elements from the disclosure and cobble them together into a
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`small “genus.”
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`In that regard, the Petition’s approach to anticipation is contrary to the well-
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`established legal principle that, to be anticipatory, a reference must disclose “all of
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`the limitations of the claims arranged or combined in the same way as recited in
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`the claims.” Vizio, Inc. v. Int’l Trade Comm’n, 605 F.3d 1330, 1342 (Fed. Cir.
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`2010) (emphasis added); see also, e.g., Net MoneyIN, Inc. v. VeriSign, Inc., 545
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`F.3d 1359, 1370 (Fed. Cir. 2008). Riedl does not do that. Instead of focusing on
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`an existing genus in Riedl that actually contains all of the elements of a claim as
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`arranged in the claim (albeit in generic form), the Petition relies on several
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`individual compounds in different parts of the reference and then combines them
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`with one small portion of a genus that was so broad that it led to a fifteen-way
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`restriction requirement. See Ex. 2007 at 282–84. That line of argument is
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`insufficient as a matter of law to establish anticipation.
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`In an effort to side-step these legal principles of anticipation, the Petition
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`refers to the Federal Circuit’s decision in Perricone v. Medicis Pharmaceutical
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`Corp., 432 F.3d 1368 (Fed. Cir. 2005), for the proposition that “[t]he anticipation
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`analysis asks solely whether the prior art reference discloses and enables the
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`claimed invention, and not how the prior art characterizes that disclosure or
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`whether alternatives are also disclosed.” Pet. at 15–16. That is beside the point.
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`Perricone involved prior art that actually recited the claimed invention. See 432
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`F.3d at 1376 (r