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`IPR2018-00125
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`Patent Owner’s Corrected Preliminary Response
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`Filed on behalf of Patent Owner Gilead Pharmasset LLC by:
`Dorothy P. Whelan (Reg. No. 33,814)
`David L. Cavanaugh (Reg. No. 36,476)
`Michael J. Kane (Reg. No. 39,722)
`Emily R. Whelan (Reg. No. 50,391)
`W. Chad Shear (Reg. No. 47,938)
`Samantak Ghosh (Reg. No. L1032)
`FISH & RICHARDSON P.C.
`E. Ross Cohen (Reg. No. 72,115)
`60 South Sixth Street, Suite 3200
`WILMER CUTLER PICKERING
`Minneapolis, MN 55402
`HALE AND DORR LLP
`1875 Pennsylvania Ave., NW
`Washington, DC 20006
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________________________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________________________________
`INITIATIVE FOR MEDICINES, ACCESS & KNOWLEDGE (I-MAK), INC.,
`Petitioner,
`v.
`GILEAD PHARMASSET LLC,
`Patent Owner.
`____________________________________________
`Case IPR2018-00125
`Patent 8,633,309
`____________________________________________
`PATENT OWNER’S CORRECTED PRELIMINARY RESPONSE
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`IPR2018-00125
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`Patent Owner’s Corrected Preliminary Response
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`TABLE OF CONTENTS
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`I.
`II.
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`Page
`INTRODUCTION ............................................................................................ 1
`TECHNOLOGY BACKGROUND ................................................................. 3
`A.
`Sofosbuvir Revolutionized the Standard of Care for Hepatitis C
`Virus Infection ............................................................................................ 3
`Nucleosides and Nucleotides ...................................................................... 5
`B.
`Stereoisomers and Diastereomers .............................................................. 6
`C.
`Sofosbuvir Is a Nucleoside Phosphoramidate Prodrug .............................. 8
`D.
`III. THE CLAIMED INVENTION ...................................................................... 10
`A. Overview of the ’309 Patent ..................................................................... 10
`B.
`Prosecution History .................................................................................. 12
`IV. PERSON OF ORDINARY SKILL IN THE ART ......................................... 15
`V. CLAIM CONSTRUCTION ........................................................................... 15
`VI. PETITIONER’S ASSERTED PRIOR ART REFERENCES ........................ 17
`A.
`Sofia ’634 ................................................................................................. 17
`B.
`Congiatu .................................................................................................... 18
`C.
`Clark ’147 ................................................................................................. 20
`VII. GROUND ONE – CLAIMS 1-12 ARE NOT ANTICIPATED BY
`SOFIA ’634 ................................................................................................... 20
`Petitioner’s Anticipation Theory Fails Because It Has Not Shown
`That Sofia ’634 Expressly or Inherently Teaches the Purity
`Limitations Required by Each of the ’309 Patent Claims ........................ 21
`Petitioner Cannot Ignore the Purity Limitations ...................................... 24
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`A.
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`B.
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`VIII. GROUND TWO – CLAIMS 1-12 ARE NOT OBVIOUS IN VIEW
`OF SOFIA ’634 AND CONGIATU .............................................................. 28
`Petitioner’s Obviousness Theory Fails Because It Has Not
`Established That Sofia ’634 and Congiatu Teach or Suggest Every
`Element of the ’309 Patent Claims ........................................................... 28
`Petitioner Has Failed to Establish a POSA’s Motivation to
`Combine Sofia ’634 with Congiatu, or That a POSA Would Have
`Had a Reasonable Expectation of Success in Doing So .......................... 32
`Petitioner’s Prosecution History Arguments Amount to Nothing
`More Than a Conclusory Disagreement with the Examiner .................... 35
`IX. GROUND THREE – CLAIMS 1-12 ARE NOT OBVIOUS IN VIEW
`OF CLARK ’147 AND CONGIATU ............................................................ 37
`A. Neither Clark ’147 nor Congiatu Teaches or Suggests the
`Compounds Recited in the ’309 Patent Claims ........................................ 38
`Neither Clark ‘147 nor Congiatu Teaches or Suggests the Purity
`Limitations ................................................................................................ 40
`Petitioner Has Failed to Establish a POSA’s Motivation to
`Combine Clark ’147 with Congiatu, or That a POSA Would Have
`Had a Reasonable Expectation of Success in Doing So .......................... 43
`Petitioner’s Prosecution History Arguments Amount to Nothing
`More Than a Conclusory Disagreement with the Examiner .................... 45
`X. THE PETITION SHOULD BE DENIED UNDER § 325(d) ........................ 47
`XI. PRESERVATION OF RIGHTS UNDER OIL STATES .............................. 51
`XII. CONCLUSION .............................................................................................. 51
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`TABLE OF AUTHORITIES
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` Page(s)
`
`Federal Cases
`Akzo N.V. v. U.S. International Trade Commission,
`808 F.2d 1471 (Fed. Cir. 1986) .......................................................................... 30
`In re Anthony,
`414 F.2d 1383 (C.C.P.A. 1969) .......................................................................... 26
`Apotex Inc. v. OSI Pharmaceuticals, Inc.,
`No. IPR2016-01284, Paper 8 (P.T.A.B. Jan. 9, 2017) ....................................... 48
`In re Baird,
`16 F.3d 380 (Fed. Cir. 1994) .............................................................................. 39
`Bettcher Industries v. Bunzl USA, Inc.,
`661 F.3d 629 (Fed. Cir. 2011) ...................................................................... 22, 23
`Bicon, Inc. v. Straumann Co.,
`441 F.3d 945 (Fed. Cir. 2006) ............................................................................ 16
`CFMT, Inc. v. YieldUp International Corp.,
`349 F.3d 1333 (Fed. Cir. 2003) .......................................................................... 28
`Coalition for Affordable Drugs VII LLC v. Pozen Inc.,
`No. IPR2015-01344, 2015 Pat. App. LEXIS 12669 (P.T.A.B. Dec.
`17, 2015) ....................................................................................................... 23, 25
`Cuozzo Speed Technologies, LLC v. Lee,
`136 S.Ct. 2131 (2016) ......................................................................................... 15
`Daiichi Sankyo Co. v. Matrix Laboratories, Ltd.,
`619 F.3d 1346 (Fed. Cir. 2010) .......................................................................... 39
`Eli Lilly & Co. v. Board of Regents of University of Washington,
`334 F.3d 1264 (Fed. Cir. 2003) .......................................................................... 39
`Forest Laboratories, Inc. v. Ivax Pharmaceuticals, Inc.,
`501 F.3d 1263 (Fed. Cir. 2007) .......................................................................... 27
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`Hospira, Inc. v. Genentech, Inc.,
`No. IPR2017-00739, 2017 Pat. App. LEXIS 10044 (P.T.A.B. July
`27, 2017) ............................................................................................................. 50
`Innogenetics, N.V. v. Abbott Laboratories,
`512 F.3d 1363 (Fed. Cir. 2008) .................................................................... 33, 44
`Insite Vision Inc. v. Sandoz, Inc.,
`783 F.3d 853 (Fed. Cir. 2015) ............................................................................ 32
`Intelligent Bio-Systems, Inc. v. Illumina Cambridge, Ltd.,
`821 F.3d 1359 (Fed. Cir. 2016) .................................................................... 34, 45
`InTouch Technologies, Inc. v. VGO Communications, Inc.,
`751 F.3d 1327 (Fed. Cir. 2014) .................................................................... 33, 44
`King Pharmaceuticals, Inc. v Eon Labs, Inc.,
`616 F.3d 1267 (Fed Cir. 2010) ..................................................................... 21, 22
`In re Kotzab,
`217 F.3d 1365 (Fed. Cir. 2000) .................................................................... 32, 33
`KSR International Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 30, 42
`Lantech, Inc. v. Keip Machine Co.,
`32 F.3d 542 (Fed. Cir. 1994) .............................................................................. 27
`Medichem, S.A. v. Rolabo, S.L.,
`437 F.3d 1157 (Fed. Cir. 2006) .......................................................................... 31
`In re Miller,
`441 F.2d 689 (C.C.P.A. 1971) ............................................................................ 25
`Neil Ziegman, N.P.Z., Inc. v. Stephens,
`No. IPR2015-01860, 2016 Pat. App. LEXIS 1127 (P.T.A.B. Feb.
`24, 2016) ............................................................................................................. 49
`Prism Pharma Co. v. Choongwae Pharma Corp.,
`No. IPR2014-00315, 2014 Pat. App. LEXIS 4429 (P.T.A.B. July
`8, 2014) ............................................................................................................... 48
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`Oil States Energy Services, LLC v. Greene’s Energy Group, LLC,
`No. 16-712 (U.S. cert. granted June 12, 2017) ................................................... 51
`Otsuka Pharmaceutical Co. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012) .......................................................................... 38
`PAR Pharmaceutical, Inc. v. TWI Pharmaceuticals., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) .................................................................... 29, 41
`Personal Web Technologies, LLC v. Apple, Inc.,
`848 F.3d 987 (Fed. Cir. 2017) ............................................................................ 29
`Pitney Bowes, Inc. v. Hewlett-Packard Co.,
`182 F.3d 1298 (Fed. Cir. 1999) .................................................................... 16, 25
`Sanofi-Synthelabo v. Apotex, Inc.,
`550 F.3d 1075 (Fed. Cir. 2008) .......................................................................... 27
`In re Stepan Co.,
`868 F.3d 1342 (Fed. Cir. 2017) .................................................................... 34, 45
`In re Translogic Technolgy, Inc.,
`504 F.3d 1249 (Fed. Cir. 2007) .......................................................................... 16
`Trintec Industries, Inc. v. Top-U.S.A. Corp.,
`295 F.3d 1292 (Fed. Cir. 2002) .......................................................................... 24
`Unified Patents Inc. v. Berman,
`No. IPR2016-01571, 2016 Pat. App. LEXIS 13480 (P.T.A.B. Dec.
`14, 2016) ....................................................................................................... 48, 49
`W.L. Gore & Associates, Inc. v. Garlock,
`721 F.2d 1540 (Fed. Cir. 1983) .......................................................................... 31
`In re Wilson,
`424 F.2d 1382 (C.C.P.A. 1970) .................................................................... 16, 24
`Wowza Media Systems, LLC v. Adobe Systems Inc.,
`No. IPR2013-00054, 2013 Pat. App. LEXIS 9471 (P.T.A.B. Apr.
`8, 2013) ............................................................................................................... 35
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`Federal Statutes
`35 U.S.C. § 325(d) ................................................................................................... 47
`Regulations
`37 C.F.R. § 42.65(a) ........................................................................................... 23, 25
`37 C.F.R. § 42.100(b) .............................................................................................. 15
`37 C.F.R. § 42.104(b)(4) .................................................................................... 21, 29
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`INTRODUCTION
`The Petition filed by Initiative for Medicines, Access & Knowledge
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`(“Petitioner”) purports to challenge each of the claims of U.S. Patent No.
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`8,633,309 (“the ’309 patent”) on one anticipation and two obviousness grounds.
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`This Petition, however, is fundamentally flawed: it does not address certain
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`important claim limitations at all and, as to other limitations, merely repeats
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`arguments overcome during prosecution without providing any new evidence that
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`can support reconsideration. Because the Petitioner has fallen well short of
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`demonstrating a reasonable likelihood of success on any of the grounds, the Board
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`should deny the Petition.
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`The ’309 patent claims recite a compound of formula 4, that is at least 97%
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`pure single isomer, wherein at least 97% of the compound is the SP-isomer (SP-4),
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`and no more than 3% is the RP-isomer (RP-4). The SP-4 is sofosbuvir, a nucleoside
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`phosphoramidate prodrug that is Gilead’s life-saving treatment for Hepatitis C.
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`Petitioner’s anticipation challenge (Ground One) relies on the Sofia ’634 PCT
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`application (Ex. 1005), which Petitioner admits, does not expressly disclose the
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`’309 patent’s 97% purity limitation. Moreover, Petitioner does not address at all
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`the limitation of “not more than 3% of the RP stereoisomer.” Petitioner tries to
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`avoid this fatal defect by suggesting that these claim limitations can be ignored,
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`demonstrating a fundamental misunderstanding of the legal requirements for a
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`disclosure to be anticipatory. Contrary to Petitioner’s assertion, these purity
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`limitations are not “irrelevant.” They are important elements defining the metes
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`and bounds of the ’309 patent claims, and must be considered in the anticipation
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`analysis.
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`Petitioner’s obviousness theories (Grounds Two and Three) are similarly
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`flawed because Petitioner’s asserted prior art combinations fail to teach or suggest
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`each of the ’309 claim limitations, the most basic prerequisite for showing prima
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`facie obviousness. Again, neither of Petitioner’s asserted prior art combinations
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`teaches or suggests the purity limitations. Remarkably, Petitioner’s combination of
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`Clark ’147 (Ex. 1007) and Congiatu (Ex. 1006) fails to teach or suggest any of the
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`limitations of independent claim 1.
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`Moreover, Petitioner provides nothing more than conclusory, boilerplate
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`statements that a person of ordinary skill in the art would have been motivated to
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`combine prior art references to achieve the claimed invention, or had a reasonable
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`expectation of success in doing so. The biased declaration of Petitioner’s expert,
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`Dr. Fortunak, is equally conclusory and consists of nothing more than a word-for-
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`word restatement of the Petition. Such statements are insufficient to make a prima
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`facie showing of obviousness.
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`Indeed, Dr. Fortunak is not an independent expert. Rather, he is an I-MAK
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`employee whose real objective is to eliminate pharmaceutical patents. See EX.
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`1002, ¶22; EX. 2001; EX. 2002. Dr. Fortunak fails to offer a reasoned scientific
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`explanation, backed by objective facts, for any of his opinions. Instead, he offers
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`only vague, conclusory statements regarding what he believes was known and
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`what he believes a person of ordinary skill would have done.
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`Finally, the Board should reject the Petition pursuant to 35 U.S.C. § 325(d).
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`For each of its asserted grounds, Petitioner relies on the same or substantially the
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`same prior art references and arguments that were before the Examiner during the
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`’309 patent’s prosecution. Petitioner seeks a different result without identifying
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`any new evidence or errors in the Examiner’s analysis.
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`The Board should deny the Petition.
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`II. TECHNOLOGY BACKGROUND
`A.
`Sofosbuvir Revolutionized the Standard of Care for Hepatitis C
`Virus Infection
`Hepatitis C virus (“HCV”) infection is a major health problem that can cause
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`potentially severe liver damage. As of 2009, “2-15% of the world’s population”
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`were infected, and there were an “estimated 4.5 million infected people in the
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`United States alone.” Ex. 1001 at 1:21-26. At the time of the invention, the
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`standard of care for HCV infection entailed recombinant interferon-α injections,
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`alone or in combination with the nucleoside analog, ribavirin, for 48 weeks. Ex.
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`2003 at 75. However, this lengthy treatment regimen was effective in only 40-60%
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`of the patients, depending on the viral genotype infecting them. See Ex. 2004 at
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`7202. Additionally, interferon produced such severe side effects—e.g., flu-like
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`symptoms, fatigue, depression—that many patients did not complete or even start
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`the therapy. Ex. 2005 at 24. Therefore, “there [was] an urgent need for improved
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`therapeutic agents that effectively combat[ed] chronic HCV infection.” Ex. 1001
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`at 1:41-43.
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`As we know now, sofosbuvir, a nucleoside phosphoramidate prodrug, which
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`is recited in the claims of the ’309 patent as compound SP-4, revolutionized the
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`standard of care. Sofosbuvir is a potent antiviral agent that has been approved by
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`the U.S. Food and Drug Administration (FDA) for treatment of HCV in Gilead’s
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`products Sovaldi®, Harvoni®, Epclusa®, and Vosevi®. Sofosbuvir’s first
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`approval (Sovaldi®) was hailed throughout the scientific and popular press,
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`including the front pages of the New York Times and Wall Street Journal, and was
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`recognized as a “game changer” for the treatment of HCV. See Ex. 2006; Ex.
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`2007; Ex. 2008. For the first time, many patients could now be cured of HCV
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`without interferon. See EX. 2009 at 65. Just ten months after the approval of
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`Sovaldi®, the FDA approved Harvoni®, which combines sofosbuvir with another
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`drug to cure 95% of the patients who take it, in as little as 8 weeks, without
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`subjecting the patients to interferon. See id.
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`B. Nucleosides and Nucleotides
`A nucleoside is made of two parts: an aromatic heterocyclic base (also
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`referred to as a “nucleobase” or, simply a “base”) and a five-membered sugar ring
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`(e.g., a ribose or a deoxyribose). See Ex. 2010 at 5-6. When the five-membered
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`sugar ring is a ribose, the nucleoside is called a “ribonucleoside” (shown below);
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`when the sugar ring is a deoxyribose, it is called a “deoxyribonucleoside.” Id. The
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`naturally-occurring bases include purines, such as guanine (G) and adenine (A);
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`and pyrimidines, such as cytosine (C), thymine (T), and uracil (U). Id.
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`The Pyrimidines
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`5
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`The Purines
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`A nucleotide is made up of (a) a nucleoside and (b) one or more phosphate
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`groups. See id. A ribonucleotide is illustrated below:
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`Each of the nucleoside mono-, di-, and triphosphates is a nucleotide.
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`Naturally occurring nucleosides are the building blocks of DNA and RNA,
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`but they can be modified in many ways to create nucleoside analogs. For example,
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`nucleoside analogs can involve modifications at one or more positions of the base,
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`the sugar, the attached phosphate group, or a combination of these positions. See
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`Ex. 2011 at 447-48, 450, 454.
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`C.
`Stereoisomers and Diastereomers
`Molecules that share the same molecular formula (i.e. molecules with the
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`same atomic composition), but differ in their atomic bonding or in the three-
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`dimensional arrangement of their atoms are referred to as “isomers.” See Ex. 2012
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`at 5; Ex. 2013 at 7. Isomers that possess the same atom-to-atom bonds, but
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`different three-dimensional arrangements of those atoms, are called
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`“stereoisomers,” shown in the generic example below. See Ex. 2012 at 10; Ex.
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`2013 at 9.
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`A “stereogenic center” is any atom in a molecule for which exchanging two groups
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`connected to that atom creates a different stereoisomer. See Ex. 2012 at 4, 7-9.
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`For example, in the molecules shown above, the carbon atom is a stereogenic
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`center.
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`“Diastereomers” are pairs of stereoisomers that are non-superimposable non-
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`mirror images of each other. See Ex. 2012 at 3; Ex. 2013 at 6. Diastereomers may
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`contain one or more stereogenic centers that do not have a plane of symmetry,
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`referred to as chiral centers. See Ex. 2012 at 2; Ex. 2013 at 5. Depending upon the
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`configuration of these groups around the chiral center, it is either designated as (R)
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`or (S). See Ex. 2013 at 8.
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`D.
`Sofosbuvir Is a Nucleoside Phosphoramidate Prodrug
`Sofosbuvir is a nucleoside phosphoramidate prodrug having the structure
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`shown below. A prodrug is a modification of a drug that is sufficiently soluble and
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`can cross the cell membranes of target cells, but that, upon administration to the
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`human body, is converted to the biologically active product by some chemical or
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`enzymatic mechanism. Ex. 2014 at 1-2. In sofosbuvir, the nucleoside portion is a
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`ribonucleoside, which is modified from its natural state at the 2’-position of the
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`sugar. In place of the hydrogen (up) and hydroxyl (down) at that position,
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`sofosbuvir contains a methyl group (up) and a fluorine atom (down). Sofosbuvir
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`has a uracil base. The prodrug portion comprises a phosphoramidate moiety
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`attached to the 5’-position of the nucleoside analog. A phosphoramidate is a
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`moiety in which one hydroxyl group of a phosphate is replaced by an amine group.
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`In sofosbuvir, the phosphoramidate is isopropyl alanate phenyl phosphoramidate.
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`The phosphoramidate prodrug modification in sofosbuvir facilitates
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`treatment of HCV by improving uptake of the active nucleoside analog to the liver.
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`See Ex. 2004 at 7206-08. Following oral administration, the compound is
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`delivered to the target liver cells, where it is metabolized to the corresponding
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`monophosphate nucleotide and subsequently converted to the di- and then
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`triphosphate. Id. The triphosphate inhibits the NS5B polymerase enzyme in HCV,
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`thereby preventing viral replication. See id. at 7202-03.
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`The chemical structure of sofosbuvir has a number of stereogenic or chiral
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`centers, where changing the orientation of the groups would lead to a different
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`stereoisomer. One of these stereogenic centers is the phosphorus atom (P) in the
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`phosphoramidate group. Sofosbuvir has (S) orientation at the P, which is
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`sometimes abbreviated as SP-4. Ex. 1001 at 5:1-12. The diastereomer of
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`sofosbuvir has (R) orientation at the P, and is sometimes referred to as RP-4. Id. at
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`5:12-23.
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`III. THE CLAIMED INVENTION
`A. Overview of the ’309 Patent
`The ’309 patent, titled “Nucleoside Phosphoramidates,” is directed generally
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`to the treatment of HCV infection. The ’309 patent specification discloses a
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`compound represented by formula 4 and its respective phosphorus-based
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`diastereomers, represented by formulas SP-4 and RP-4. Ex. 1001 at 4:52-54. The
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`respective chemical structures are shown below:
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`Id. at col. 4:57-5:24. The compound of formula SP-4 is sofosbuvir.
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`The ’309 patent discloses methods of synthesizing the formula 4 compound
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`as a diastereomeric mixture of SP-4 and RP-4. Id. at 31:60-33:56. It further
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`discloses methods of obtaining substantially pure SP-4 from the mixture of
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`diastereomers by chromatography, and by crystallization of the individual
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`stereoisomers. Id. at 36:3-12 (describing crystallization process that resulted in
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`“>99% pure SP-4”); id. at 72:34-61 (describing HPLC purification conditions that
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`resulted in 99.5% pure SP-4). Additionally, the patent teaches methods of
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`generating substantially pure isomers by diastereoselective synthesis. See, e.g., id.
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`at 49:25-50:7 (describing processes for stereoselective synthesis of the SP-4
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`enantiomer, resulting in 97% “chiral purity”). The potency of each of the
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`compounds of formula 4, RP-4, and SP-4 was demonstrated by viral “replicon”
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`assays. See id. at 75:30-56 (describing biological activity tests).
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`Claim 1, the sole independent claim, reads:
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`A compound represented by the formula (4):
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`
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`wherein P* represents a chiral phosphorus atom and
`wherein the compound is at least 97% of the SP
`stereoisomer represented by the formula (SP-4):
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`and not more than 3% of the RP stereoisomer represented
`by the formula (RP-4):
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`Id. at 76:2-47. Dependent claims 2 and 3 recite at least 98% and 99% SP-4,
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`respectively (and likewise decrease RP-4 to at most 2% and 1%, respectively). The
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`remaining dependent claims cover pharmaceutical compositions comprising
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`compounds according to claims 1-3 (claims 4-6); and methods of treating HCV
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`comprising administering such compounds to a human, alone or combined with
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`another antiviral agent (claims 7-12).
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`B.
`Prosecution History
`The ’309 patent originated from U.S. Application No. 13/738,425 (“the ’425
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`application”), which was filed on January 10, 2013. The issued claims of the ’309
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`patent are unchanged from the original claims in the ’425 application.
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`On April 4, 2013, the Examiner issued a non-final rejection finding the
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`pending claims obvious over Sofia, 2nd International Workshop on HCV-
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`Resistance and New Compounds, October 31, 2007 (“Sofia 2007”). Ex. 1004 at
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`12-13. Sofia 2007 disclosed a genus of nucleoside phosphoramidates for treatment
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`of HCV. The Examiner found that the pending claims would have been obvious
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`over Sofia 2007, which “teaches a phosphoramidate prodrug of formula
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`wherein R3 is [an] isopropyl group . . . , which is a mixture of Sp and Rp
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`stereoisomers.” Id. at 12. The Examiner also issued a non-statutory double
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`patenting rejection based on related U.S. Patent No. 7,964,580 (“the ’580 patent”).
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`Id. at 13-15.
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`In a response dated May 15, 2013, Applicant argued that the Examiner’s
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`unsupported findings were insufficient to establish a prima facie case of
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`obviousness. Ex. 1004 at 20-24.1 Among other things, the Applicant argued Sofia
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`2007 did not teach or suggest (1) the stereoisomerism of any of the disclosed genus
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`of compounds, (2) the separation of stereoisomers, or (3) “that one skilled in the art
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`should obtain either the RP or SP stereoisomer of any compound to a specific
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`degree of stereoisomeric purity.” Id. at 22-23. Finally, the Applicant argued that,
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`even if the Examiner had established a prima facie case of obviousness, the
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`increased activity of the SP-4 compound over the RP-4 compound was unexpected,
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`thereby rebutting any prima facie showing. Id. at 24. The Applicant also filed a
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`terminal disclaimer to address the Examiner’s non-statutory double patenting
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`rejection. Id.
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`1 Applicant refiled the Office Action Response on May 21, 2013, after the May 15
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`Response was found non-compliant. Ex. 1004 at 27-36. The newly filed response
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`was substantively identical to the original.
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`On July 10, 2013, the Examiner withdrew the outstanding obviousness and
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`obviousness-type double patenting rejections. Ex. 1004 at 39. The Examiner,
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`however, issued a second double patenting rejection over a co-pending application,
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`which the Applicant overcame by filing another terminal disclaimer. Id. at 40, 47.
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`The Examiner issued the Notice of Allowance on September 16, 2013. Ex.
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`1004 at 49-58. The Examiner stated:
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`The claimed invention is novel and non-obvious over the
`prior art. While it is known in the art to make
`phosphoramidate compounds such as
`the
`instantly
`claimed ones, for example as described in US patent
`7964580 (of record in previous action) and furthermore
`to resolve chiral compounds into individual enantiomers,
`Applicant has discovered that the SP enantiomer of the
`claimed compound is unexpectedly more potent in
`inhibiting HCV replication as disclosed on p. 97 of the
`specification as originally filed. Therefore any prima
`facie case of obviousness is overcome by this finding of
`unexpected results. For these reasons the claims meet the
`requirements of 35 USC 102 and 103.
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`Id. at 56. The ’580 patent—referenced previously in prosecution and again in the
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`Examiner’s Notice of Allowance—issued from the U.S. equivalent application of
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`WO 2008/121634 (“Sofia ’634”), which was cited in the ’309 patent specification.
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`Ex. 1001 at 4:42-46.
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`The ’309 patent issued on January 21, 2014.
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`IV. PERSON OF ORDINARY SKILL IN THE ART
`A person of ordinary skill in the art (“POSA”) would have either (1) a Ph.D.
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`in chemistry or a closely related field with some experience in an academic or
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`industry laboratory focusing on drug discovery or development, including
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`compound purification, and would have some familiarity with the development of
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`antiviral drugs, or work in collaboration with someone who has expertise in the
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`development of antiviral drugs; or (2) a Bachelor’s or Master’s degree in chemistry
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`or a closely related field with significant experience in an academic or industrial
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`laboratory focusing on drug discovery, including compound purification, and some
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`familiarity with development of antiviral drugs, or work in collaboration with
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`someone who has expertise in the development of antiviral drugs.
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`This definition differs from Petitioner’s asserted definition, see Paper 2 at 9,
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`in that it recognizes that the POSA is a chemist who may consult and collaborate as
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`needed with others having relevant knowledge regarding antiviral drug
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`development. This difference does not affect any of the arguments set out below.
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`V. CLAIM CONSTRUCTION
`In an IPR proceeding, the terms of the challenged claims are to be given
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`their broadest reasonable interpretation in light of the specification as commonly
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`understood by those of ordinary skill in the art. See 37 C.F.R. § 42.100(b); Cuozzo
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`Speed Techs., LLC v. Lee, 136 S.Ct. 2131 (2016). Petitioner does not propose a
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`definition for any term. See Paper 2 at 10 (“[T]here is no reason to give any of the
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`terms of the claims of the ’309 [patent] a meaning other than their ordinary and
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`accustomed meaning.”). For the purposes of this Preliminary Response, Patent
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`Owner does not propose any claim construction. Hence, the terms of the
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`challenged claims should be given their ordinary and customary meaning. See In
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`re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007).
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`As discussed below, many of Petitioner’s arguments seek to ignore or render
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`meaningless certain claim limitations. Although not specifically labeled “claim
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`construction” arguments, these assertions contravene the well-established canon
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`that “claims are interpreted with an eye toward giving effect to all terms in the
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`claim.” See Bicon, Inc. v. Straumann Co., 441 F.3d 945, 950 (Fed. Cir. 2006); see
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`also In re Wilson, 424 F.2d 1382, 1385 (C.C.P.A. 1970) (“All words in a claim
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`must be considered in judging the patentability of that claim against the prior art.”).
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`According to these established principles, all limitations in the challenged claims
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`must be given weight and meaning. See Bicon, 441 F.3d at 950; cf. Pitney Bowes,
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`Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305 (Fed. Cir. 1999) (explaining that
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`a claim preamble constitutes a claim limitation—and must be given patentable
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`weight—when it helps define the “complete invention” or “is ‘necessary to give
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