`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`Filed on behalf of Patent Owner Gilead Pharmasset LLC by:
`David L. Cavanaugh (Reg. No. 36,476)
`Dorothy P. Whelan (Reg. No. 33,814)
`Emily R. Whelan (Reg. No. 50,391)
`Michael J. Kane (Reg. No. 39,722)
`Samantak Ghosh (Reg. No. L1032)
`W. Chad Shear (Reg. No. 47,938)
`WILMER CUTLER PICKERING
`FISH & RICHARDSON P.C.
`HALE AND DORR LLP
`60 South Sixth Street, Suite 3200
`60 State Street
`Minneapolis, MN 55402
`Boston, MA 02109
`
`
`
`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 IPR2018-00390
`Patent 8,889,159 B2
`____________________________________________
`PATENT OWNER’S PRELIMINARY RESPONSE
`
`

`

`
`
`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`TABLE OF CONTENTS
`
`I.
`II.
`
`Page
`INTRODUCTION ........................................................................................... 1
`TECHNOLOGY BACKGROUND ................................................................. 3
`A. Sovaldi® Was a “Game-Changing” Treatment for HCV ............................. 3
`B. Solid Forms of Pharmaceutical Compounds ................................................. 5
`C. Crystalline Forms of Sofosbuvir ................................................................... 6
`D. Formulations of Sofosbuvir ........................................................................... 6
`III. THE ’159 PATENT ......................................................................................... 7
`A. Overview of the ’159 Patent .......................................................................... 7
`B. Prosecution History ....................................................................................... 9
`IV. PERSON OF ORDINARY SKILL IN THE ART ........................................ 10
`V.
`CLAIM CONSTRUCTION .......................................................................... 11
`VI. PETITIONER’S ASSERTED REFERENCES ............................................. 11
`A. Ross ’645 ..................................................................................................... 11
`B. Ross ’257 ..................................................................................................... 12
`VII. THE PETITION SHOULD BE DENIED BECAUSE NO GROUND
`HAS A REASONABLE LIKELIHOOD OF SUCCESS .............................. 12
`A. Ground 1: Claims 1-37 Are Not Anticipated by Ross ’645 ....................... 12
`1.
`Ross ’645 Fails to Disclose All the Limitations of the ’159
`Patent Claims ....................................................................................... 13
`
`2.
`
`Petitioner Fails to Assert Anticipation with Particularity ................... 23
`
`B. Ground 2: Claims 1-37 Are Not Obvious Over Ross ’645 ........................ 25
`
`
`
`i
`
`

`

`
`
`
`
`1.
`
`2.
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`Petitioner Fails to Articulate its Obviousness Theory with
`Particularity ......................................................................................... 26
`
`The Challenged Claims Are Not Obvious Over Ross ’645,
`Alone or in Combination with the Alleged “Background
`Knowledge” ......................................................................................... 28
`
`C. Ground 3: Claims 1-37 Are Not Anticipated by Ross ’257 ....................... 44
`1.
`Ross ’257 Does Not Disclose the Claimed Crystalline Form of
`Sofosbuvir ........................................................................................... 44
`
`2.
`
`Petitioner Fails to Assert Anticipation with Particularity ................... 51
`
`D. Ground 4: Claims 1-37 Are Not Obvious Over Ross ’257 ......................... 52
`1.
`Petitioner Fails to Articulate its Obviousness Theory with
`Particularity ......................................................................................... 52
`
`2.
`
`The Challenged Claims Are Not Obvious Over Ross ’257,
`Alone or in Combination with the Alleged “Background
`Knowledge” ......................................................................................... 53
`
`VIII. GROUNDS 3 AND 4 SHOULD BE DENIED UNDER 35 U.S.C. §
`325(d) ............................................................................................................. 60
`IX. CONCLUSION .............................................................................................. 62
`
`
`
`
`
`ii
`
`

`

`
`
`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`
`Federal Cases
`Allergan, Inc. v. Apotex Inc., 754 F.3d 952 (Fed. Cir. 2014) .................................. 41
`Atofina v. Great Lakes Chemical Corp., 441 F.3d 991 (Fed. Cir. 2006) .........passim
`Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc., 246 F.3d
`1368 (Fed. Cir. 2001)............................................................................... 19, 48
`CallCopy, Inc. v. Verint Americas, Inc., No. IPR2013-00486, 2013
`WL 8595753 (P.T.A.B. Feb. 5, 2014) ................................................. 2, 24, 26
`Complex Innovations, LLC v. Amgen Inc., No. IPR2016-00085, Paper
`8 (P.T.A.B. Apr. 13, 2016) .....................................................................passim
`Complex Innovations, LLC v. Astrazeneca AB, No. IPR2017-00631,
`2017 WL 3142064 (P.T.A.B. July 24, 2017) .............................. 16, 20, 47, 49
`Duro-Last, Inc. v. Custom Seal, Inc., 321 F.3d 1098 (Fed. Cir. 2003) ................... 26
`E.I. du Pont de Nemous & Co. v. Furanix Technologies B.V., No.
`IPR2015-01838, 2017 Pat. App. LEXIS 12978 (P.T.A.B.
`March 3, 2017) ............................................................................................... 31
`Ex Parte Fukuzumi, Appeal No. 2009-012321, 2010 WL 3410867
`(B.P.A.I. Aug. 27, 2010) ................................................................................ 32
`Ex Parte Liu, Appeal No. 2013-004753, 2014 WL 6998377 (P.T.A.B.
`Dec. 10, 2014) .................................................................................... 32, 33, 56
`Graco Children’s Products Inc. v. Kolcraft Enterprises, Inc., No.
`IPR2016-00810, 2016 WL 6650119 (P.T.A.B. Sept. 28, 2016) ................... 26
`Hopkins Manufacturing Corp. v. Cequent Performance Products, Inc.,
`IPR2015-00609, 2015 WL 4934184 (P.T.A.B. Aug. 14, 2015) ....... 28, 29, 41
`Hospira, Inc. v. Genentech, Inc., No. IPR2017-00739, 2017 Pat. App.
`LEXIS 10044 (P.T.A.B. July 27, 2017) ........................................................ 63
`
`
`
`iii
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`In re Armodafinil Patent Litigation, 939 F. Supp. 2d 456 (D. Del.
`2013) ........................................................................................................ 30, 56
`In re Depomed, No. 13-cv-4507, 2016 WL 7163647 (D.N.J. Sept. 30,
`2016) ........................................................................................................ 47, 55
`In re Magnum Oil Tools International, Ltd., 829 F.3d 1364 (Fed. Cir.
`2016) .................................................................................................. 31, 33, 42
`In re Nuvasive, Inc., 842 F.3d 1376 (Fed. Cir. 2016) .............................................. 36
`In re Translogic Technology, Inc., 504 F.3d 1249 (Fed. Cir. 2007) ....................... 12
`Insite Vision Inc. v. Sandoz, Inc., 783 F.3d 853 (Fed. Cir. 2015) ...................... 31, 35
`Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376 (Fed.
`Cir. 2015) ........................................................................................... 15, 20, 46
`King Pharmaceuticals, Inc. v Eon Labs, Inc., 616 F.3d 1267 (Fed Cir.
`2010) .......................................................................................................passim
`Kingbright Electronic Co. v. Cree Inc., No. IPR2015-00750, Paper 8
`(P.T.A.B. Aug. 10, 2015) .............................................................................. 29
`Lupin Ltd. v. Janssen Sciences Ireland UC, No. IPR2015-01030,
`Paper 17 (P.T.A.B. Oct. 16, 2015) ................................................................ 47
`Mylan Pharmaceuticals Inc. v. Boehringer Ingelheim International
`GmbH, No. IPR2016-01566, 2017 WL 506739 (P.T.A.B. Feb.
`3, 2017) ...................................................................................................passim
`Neil Ziegman, N.P.Z., Inc. v. Stephens, No. IPR2015-01860, 2016 Pat.
`App. LEXIS 1127 (P.T.A.B. Feb. 24, 2016) ................................................. 63
`Neptune Generics, LLC v. Nektar Therapeutics, No. IPR2016-00049,
`2016 WL 2866259 (P.T.A.B. Apr. 27, 2016) ................................................ 31
`Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359 (Fed. Cir. 2008) ................. 2, 15
`Nextec Applications, Inc. v. Brookwood Cos., 703 F. Supp. 2d 390
`(S.D.N.Y. 2010) ............................................................................................. 26
`
`
`
`iv
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`PAR Pharmaceutical, Inc. v. TWI Pharmaceuticals, Inc., 773 F.3d
`1186 (Fed. Cir. 2014)............................................................................... 44, 60
`Ruiz v. A.B. Chance Co., 357 F.3d 1270 (Fed. Cir. 2004) ....................................... 36
`Structural Rubber Products Co. v. Park Rubber Co., 749 F.2d 707
`(Fed. Cir. 1984) .......................................................................................passim
`Unified Patents Inc. v. Berman, No. IPR2016-01571, 2016 Pat. App.
`LEXIS 13480 (P.T.A.B. Dec. 14, 2016) ....................................................... 63
`Federal Statutes
`35 U.S.C. § 311(b) ................................................................................................... 27
`35 U.S.C. § 312(a)(3) ..................................................................................... 2, 24, 27
`35 U.S.C. § 325(d) ................................................................................................... 61
`Regulations
`37 C.F.R. § 42.104(b)(4) ...................................................................................passim
`Other Authorities
`MPEP § 2131.02 ...................................................................................................... 16
`MPEP § 2144.05 ...................................................................................................... 31
`
`
`
`
`v
`
`

`

`
`
`
`I.
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`INTRODUCTION
`The Petition filed by I-MAK (“Petitioner”) falls significantly short of
`
`demonstrating a reasonable likelihood of success on any of the grounds for at least
`
`the following reasons: it fails to locate each limitation of the challenged claims in
`
`the prior art; conflates anticipation with obviousness; improperly relies on
`
`“background knowledge”; and never explains why a person of ordinary skill in the
`
`art (“POSA”) would have been motivated to combine or modify the asserted
`
`references, or have had a reasonable expectation of success in achieving the
`
`claimed invention by doing so.
`
`The challenged claims of U.S. Patent No. 8,889,159 (“the ’159 patent”),
`
`which are embodied in Gilead’s groundbreaking anti-hepatitis C virus (“HCV”)
`
`treatment Sovaldi®, are directed to novel compositions comprising crystalline
`
`Form 6 of sofosbuvir and pharmaceutically acceptable excipients.
`
`In Grounds 1 and 2, Petitioner argues that Ross ’645 (EX1008) anticipates
`
`and/or renders the claims obvious. Petitioner’s anticipation challenge is facially
`
`deficient because Petitioner fails to even argue that Ross ’645 discloses each and
`
`every element of the ’159 patent claims. Instead, Petitioner relies on generic
`
`disclosures in Ross ’645 and purported background knowledge to assert that these
`
`elements were taught. See, e.g., Paper 2 at 26. Such disclosures are insufficient to
`
`establish anticipation, which requires that the prior art “must not only disclose all
`
`1
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`elements of the claim within the four corners of the document, but must also
`
`disclose those elements ‘arranged as in the claim.’” Net MoneyIN, Inc. v. VeriSign,
`
`Inc., 545 F.3d 1359, 1369 (Fed. Cir. 2008). Ross ’645’s generic disclosure
`
`(permitting 5-95% of an active ingredient) also cannot anticipate the specifically
`
`claimed compositions (requiring, for example, “about 25 to 35%” of Form 6
`
`sofosbuvir) because it does not “describe[] the claimed range with sufficient
`
`specificity.” See Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 999 (Fed. Cir.
`
`2006). Petitioner’s Ground 1 is further deficient because it conflates anticipation
`
`and obviousness (see, e.g., Paper 2 at 26, 30-31) and therefore fails to assert
`
`anticipation with particularity. 35 U.S.C. § 312(a)(3); CallCopy, Inc. v. Verint
`
`Ams., Inc., No. IPR2013-00486, 2013 WL 8595753, at *5 (P.T.A.B. Feb. 5, 2014).
`
`Petitioner’s obviousness challenge in Ground 2 similarly fails to establish
`
`that Ross ’645 teaches or suggests the claimed compositions with the recited
`
`amounts of crystalline sofosbuvir with XRPD-2θ reflections corresponding to
`
`Form 6, or the claimed excipients in the claimed amounts. Petitioner improperly
`
`tries to overcome these deficiencies of Ross ’645 by using alleged “common
`
`knowledge” that it has cherry-picked with hindsight to supply the missing
`
`elements. See, e.g., Paper 2 at 33-34. Petitioner repeatedly relies on alleged
`
`“background” references for disclosing the elements missing in Ross ’645 without
`
`including these references in the proposed ground, or clearly articulating its
`
`2
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`obviousness theory based on a specific combination of references. Further,
`
`Petitioner never explains why a POSA would have been motivated to combine this
`
`alleged “background” or “common” knowledge to arrive at the claimed
`
`compositions with any reasonable expectation of success. Id. at 27-35.
`
`Grounds 3 and 4, in which Petitioner asserts anticipation and obviousness
`
`over Ross ’257 (EX1005), respectively, are deficient for the same reasons as
`
`Grounds 1 and 2. Moreover, Grounds 3 and 4 are fatally flawed because Ross ’257
`
`never discloses or suggests Form 6 of sofosbuvir, the active ingredient in all the
`
`claimed compositions.
`
`Additionally, Ross ’257 was expressly considered by the Examiner during
`
`prosecution of the ’159 patent. Petitioner’s Grounds 3 and 4 rely on art and
`
`arguments that Patent Owner overcame during prosecution. The Board should
`
`therefore exercise its discretion under 35 U.S.C. § 325(d) to deny Grounds 3 and 4.
`
`For at least these reasons, the Board should deny this Petition.
`
`II. TECHNOLOGY BACKGROUND
`Sovaldi® Was a “Game-Changing” Treatment for HCV
`A.
`HCV infection is a major health problem that can cause potentially severe
`
`liver damage. As of 2012, an estimated 150-180 million people worldwide,
`
`including 3.2 million people in the United States, were chronically infected with
`
`HCV. EX1001 at 1:37-46. Before Sovaldi®, which embodies the claimed
`
`3
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`compositions of the ’159 patent, the standard of care for HCV infection was
`
`limited to recombinant interferon-α injections for 48 weeks, alone or in
`
`combination with the nucleoside analog ribavirin. EX2001 at 75. However, this
`
`lengthy treatment regimen was effective in fewer than half of the patients,
`
`depending on the viral genotype infecting them. EX2003 at 471. Additionally,
`
`interferon produced such severe side effects, such as fatigue, depression, and
`
`hemolytic anemia. See id. Thus, there was “a need for improved treatment
`
`regimens that are more effective, safe, tolerable, [and] shorter in duration” than the
`
`interferon treatment standard at the time of invention. EX1001 at 5:10-13.
`
`On December 6, 2013, after expedited review, the FDA approved Sovaldi®,
`
`as a once-daily oral treatment for chronic HCV infection. EX2010 at 8, 15. The
`
`active ingredient of Sovaldi® is sofosbuvir, a nucleoside phosphoramidate having
`
`the structure shown below:
`
`
`
`4
`
`

`

`
`
`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`Sovaldi®’s approval was hailed throughout the scientific and popular press,
`
`including the front pages of the New York Times and Wall Street Journal, and was
`
`recognized as a “game changer” for the treatment of HCV. EX2007; EX2008;
`
`EX2009. For the first time, many HCV patients could be treated without
`
`interferon, while others only needed to take interferon for 12 weeks. EX2007;
`
`EX2008; EX2009.
`
`Solid Forms of Pharmaceutical Compounds
`B.
`A given chemical compound may exist in multiple solid forms, depending
`
`on how the molecules of the compound are arranged in three-dimensional space.
`
`Solid-state forms may include crystalline and amorphous forms. A crystalline
`
`solid has a regularly repeating three-dimensional structure, also referred to as
`
`“three-dimensional long-range order.”1 EX2004 at 1. A compound may be
`
`capable of crystallizing in more than one crystal structure—a phenomenon known
`
`as “polymorphism.” Id. The different crystalline forms that a compound can take
`
`are known as “polymorphs.” Because of the intimate relationship between a
`
`compound’s three-dimensional structure and its properties, different solid forms of
`
`a compound can, and often do, exhibit different properties. Id. X-ray powder
`
`
`1 In contrast, amorphous solids lack such three-dimensional long-range order.
`
`EX2004 at 1.
`
`5
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`diffraction (“XRPD”), a crystallographic method, is one of the most commonly
`
`used methods for identifying and distinguishing polymorphs. EX2005 at 38-56.
`
`C. Crystalline Forms of Sofosbuvir
`The ’159 patent claims novel and advantageous compositions comprising a
`
`stable, non-hygroscopic crystalline form of sofosbuvir, Form 6. EX1001 at 46:35-
`
`49:29; id. at 8:18-26, 40-49. The challenged claims recite XRPD “2θ-reflections”
`
`that distinguish Form 6 of sofosbuvir from other crystalline forms of the
`
`compound. The ’159 patent discloses six crystalline forms of sofosbuvir,
`
`identified as Forms 1-6. Id. at 8:18-49. Form 6 of sofosbuvir is used in Gilead’s
`
`Sovaldi®.
`
`Formulations of Sofosbuvir
`D.
`Numerous factors must be considered when formulating an active
`
`ingredient, including the dose, stability, solubility, density, compressibility,
`
`excipients, amounts of excipients, methods of preparation, and bioavailability of
`
`the drug. EX1009 at 7-8. “[C]are must be taken in the selection and evaluation of
`
`additives and preparation methods to ensure that the drug delivery goals and
`
`therapeutic efficacy of the active ingredient will not be diminished.” EX1011 at 5.
`
`Developing the claimed formulations of sofosbuvir containing the particular
`
`crystalline form of sofosbuvir in the claimed amounts and the specific
`
`pharmaceutically acceptable excipients in the claimed amounts entailed extensive
`
`6
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`inventive effort. EX1001 at 8:50-56, 28:8-15, 32:6-21. The resulting formulation,
`
`which is embodied in Sovaldi®, was unexpectedly robust, highly stable, not
`
`sensitive to moisture, and had superior tablet content uniformity. Id.
`
`III. THE ’159 PATENT
`A. Overview of the ’159 Patent
`The ’159 patent, titled “Compositions and Methods for Treating Hepatitis C
`
`Virus,” is directed generally to pharmaceutical compositions of sofosbuvir for the
`
`treatment of HCV. The patent discloses compositions and unit dosage forms
`
`comprising GS-7977 (sofosbuvir) with at least one pharmaceutically acceptable
`
`excipient. EX1001 at Abstract. The patent further discloses methods for making
`
`the pharmaceutical compositions and unit dosage forms, and methods for treating a
`
`subject infected with HCV. Id.
`
`Independent claim 1 reads as follows:
`
`1. A pharmaceutical composition comprising:
`
`a) about 25% to about 35% w/w of crystalline GS-7977 having the structure
`
`
`
`7
`
`

`

`
`
`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`and
`b) at least one pharmaceutically acceptable excipient,
`
`wherein the crystalline GS-7977 has XRPD 2θ-reflections (°) at about:
`
`6.1 and 12.7.
`The XRPD 2θ-reflections recited in claim 1 correspond to crystalline sofosbuvir
`
`Form 6.
`
`Claims 2-15 depend from claim 1. They further specify the XRPD data and
`
`acceptable excipients for the claimed composition. For example, claim 15
`
`specifies a composition comprising about 33% sofosbuvir, 30% mannitol (a
`
`diluent), 30% microcrystalline cellulose (a diluent), 5% croscarmellose sodium (a
`
`disintegrant), 0.5% colloidal silicon dioxide (a glidant), and 1.5% magnesium
`
`stearate (a lubricant). Claims 33 and 34 recite methods of treating HCV infection
`
`using the composition of claim 1 and the composition of claim 1 in combination
`
`with ribavirin, respectively.
`
`Independent claim 16 recites a unit dosage form comprising about 400 mg of
`
`crystalline sofosbuvir exhibiting XRPD 2θ-reflections (°) at about 6.1 and 12.7
`
`with at least one pharmaceutically acceptable excipient. Claims 17-32 depend
`
`from claim 16. They further specify the XRPD data, the excipients, and methods
`
`of preparation for the claimed unit dosage form. For example, claim 29 specifies
`
`that the unit dosage form comprises about 400 mg sofosbuvir, 360 mg mannitol,
`
`8
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`356 mg microcrystalline cellulose, 60 mg croscarmellose sodium, 6 mg colloidal
`
`silicon dioxide, and 18 mg magnesium stearate. Claims 35-37 recite methods of
`
`treating HCV infection by administering the unit dosage form of claim 17,
`
`administering the unit dosage form of claim 17 in combination with ribavirin, and
`
`administering the unit dosage form of claim 17 in combination with ribavirin as
`
`part of an interferon-free treatment regimen, respectively.
`
`Prosecution History
`B.
`The ’159 patent originated from U.S. Application No. 13/686,664, which
`
`was filed on November 27, 2012, as a continuation-in-part of U.S. Application No.
`
`13/661,509 (abandoned), and claimed the benefit of U.S. Provisional Application
`
`No. 61/564,500 filed on November 29, 2011.
`
`On October 18, 2013, the Examiner issued a non-final rejection finding the
`
`claims obvious over Ross et al., U.S. Pub. No. 2010/0298257 (“Ross ’257”) in
`
`combination with Schubert, U.S. Pub. No. 2010/0298257 (“Schubert”), and World
`
`Health Organization “Pharmaceutical excipients – an overview including
`
`considerations for pediatric dosing” (“WHO”). EX1002 at 85. According to the
`
`Examiner, Ross ’257 disclosed a compound corresponding to the claimed
`
`structure. EX1002 at 85-86. The Examiner also raised double-patenting rejections
`
`over co-pending Application Nos. 13/661,509, 13/875,252, 13/732,725 and
`
`13/738,425. Id. at 91-94.
`
`9
`
`

`

`
`
`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`On January 21, 2014, Patent Owner amended the claims to recite crystalline
`
`sofosbuvir exhibiting XRPD 2θ-reflections corresponding to Form 6. EX1002 at
`
`108. Patent Owner argued that the amendment rendered the obviousness rejection
`
`moot because none of the cited references taught or suggested Form 6 of
`
`sofosbuvir. Id. at 108. In a Final Rejection dated March 18, 2014, the Examiner
`
`withdrew the obviousness rejection in light of Patent Owner’s amendment. Id. at
`
`114. Patent Owner subsequently filed a response and terminal disclaimers, which
`
`resolved the outstanding double-patenting objections. On July 17, 2014, the claims
`
`were allowed. Id. at 134-43.
`
`IV. PERSON OF ORDINARY SKILL IN THE ART
`A POSA at the time of the invention would have: (1) a Ph.D. in chemistry,
`
`pharmacy or a closely related field, with some experience in an academic or
`
`industrial laboratory focusing on drug formulation, and would also have some
`
`familiarity with the clinical development of antiviral drugs, or work in
`
`collaboration with someone who has expertise in the clinical development of
`
`antiviral drugs; or (2) a Bachelor’s or Master’s degree in chemistry, pharmacy, or a
`
`closely related field, with significant experience in an academic or industrial
`
`laboratory focusing on drug formulation, and some familiarity with clinical
`
`development of antiviral drugs, or work in collaboration with someone who has
`
`expertise in the clinical development of antiviral drugs.
`
`10
`
`

`

`
`
`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`This definition primarily differs from Petitioner’s asserted definition in that
`
`it recognizes that the POSA can be a pharmacist or a formulator who may consult
`
`and collaborate as needed with others having relevant knowledge regarding the
`
`clinical development of antiviral drugs. Paper 2 at 7-8. This difference does not
`
`affect the arguments set out below.
`
`V. CLAIM CONSTRUCTION
`Petitioner does not propose a definition of any term. Paper 2 at 8. For the
`
`purposes of this Preliminary Response, Patent Owner does not propose any claim
`
`construction. The terms of the challenged claims should be given their ordinary
`
`and customary meaning. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed.
`
`Cir. 2007).
`
`VI. PETITIONER’S ASSERTED REFERENCES
`A. Ross ’645
`Ross ’645 is a PCT application published on October 6, 2011. EX1008.
`
`The application is directed to nucleoside phosphoramidates and their use for
`
`treating HCV. Id. at 2. Ross ’645 discloses compounds 4, RP-4 and SP-4
`
`(sofosbuvir). Id. at 18:17-20:24, 116:1-117:15. Ross ’645 further teaches methods
`
`of making sofosbuvir, including various solid forms of sofosbuvir. Id. at 45-56,
`
`91-114. It discloses that sofosbuvir exists in both amorphous and crystalline
`
`forms, including at least six crystalline forms (Forms 1-6). Id. at 8-9. Elsewhere,
`
`11
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`Ross ’645 states that “[a] typical preparation will contain from about 5% to about
`
`95% active compound or compounds (w/w),” without referencing any specific
`
`crystalline form of sofosbuvir, let alone Form 6. EX1008, 21. Ross ’645 does not
`
`disclose or suggest the claimed formulations of the ’159 patent.
`
`B. Ross ’257
`Ross ’257 is a U.S. patent application published on November 25,
`
`2010. EX1005 at 1. Like Ross ’645, Ross ’257 is directed to nucleoside
`
`phosphoramidates and their use for treating HCV. Id. Because Ross ’257 is a
`
`parent application of Ross ’645, its disclosure is similar to that of Ross ’645.
`
`However, Ross ’257 does not disclose Form 6 of sofosbuvir. Id. at 28-29. It also
`
`does not disclose or suggest the claimed formulations of the ’159 patent. In fact,
`
`Ross ’257 was expressly considered during the prosecution of the ’159 patent, and
`
`the claims were found patentable over it. See Section III.B.
`
`VII. THE PETITION SHOULD BE DENIED BECAUSE NO GROUND
`HAS A REASONABLE LIKELIHOOD OF SUCCESS
`A. Ground 1: Claims 1-37 Are Not Anticipated by Ross ’645
`Petitioner asserts in Ground 1 that the ’159 patent claims are anticipated by
`
`Ross ’645. This argument must fail because Petitioner does not identify several
`
`limitations of the claims as being disclosed in Ross ’645. Instead, Petitioner
`
`attempts to supply the missing limitations by repeatedly referring to “background
`
`knowledge” and what was supposedly “known” in the art. Petitioner’s reliance on
`
`12
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`teachings beyond the four corners of Ross ’645 is a concession that its anticipation
`
`argument is deficient. Moreover, Petitioner’s argument conflates anticipation with
`
`obviousness and therefore does not assert anticipation with particularity.
`
`Petitioner has failed to establish that it is reasonably likely to prevail on its
`
`anticipation challenge for any challenged claim. Therefore, the Board should deny
`
`institution on Ground 1.
`
`1.
`
`Ross ’645 Fails to Disclose All the Limitations of the ’159
`Patent Claims
`a) Claim 1-2 Are Not Anticipated by Ross ’645
`Claim 1 of the ’159 patent recites “[a] pharmaceutical composition
`
`comprising: . . . about 25% to about 35% w/w of crystalline GS-7977 having the
`
`structure[:]
`
`
`[] and at least one pharmaceutically acceptable excipient, wherein the
`
`crystalline GS-7977 has XRPD 2θ-reflections (°) at about: 6.1 and 12.7.” EX1001
`
`at claim 1. Claim 2 further specifies the XRPD 2θ-reflections.
`
`13
`
`

`

`
`
`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`For Ross ’645 to anticipate claims 1 or 2, it must disclose “each and every
`
`limitation,” expressly or inherently. King Pharm., Inc. v Eon Labs., Inc., 616 F.3d
`
`1267, 1274 (Fed Cir. 2010). Petitioner argues that Ross ’645 anticipates claims 1
`
`and 2 because “the claimed range of about 25% to about 35% w/w falls within the
`
`range taught by Ross ’645 of about 5% to about 95% and there are no surprising or
`
`unexpected results from the narrower claimed range.” Paper 2 at 30-31. But
`
`Ross ’645’s generic disclosure is insufficient to anticipate the claimed
`
`compositions requiring 25-35% (w/w) crystalline sofosbuvir having the claimed
`
`XRPD 2θ-reflections.
`
`An anticipatory disclosure “must not only disclose all elements of the claim
`
`within the four corners of the document, but must also disclose those elements
`
`‘arranged as in the claim.’” Net MoneyIN, 545 F.3d at 1369-70 (explaining that a
`
`prior art reference does not anticipate if it does “not contain a discussion
`
`suggesting or linking” the distinct claim limitations). Ross ‘645’s disclosure of
`
`Form 6 of sofosbuvir and its generic disclosure that “[a] typical preparation will
`
`contain from about 5% to about 95% active compound or compounds (w/w),”
`
`EX1008 at 21, bear no relation to each other. Nowhere in Ross ‘645 is there any
`
`teaching of compositions containing about 5-95% of crystalline sofosbuvir
`
`generally (or Form 6 in particular). Petitioner thus fails to assert, let alone
`
`14
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`demonstrate, that Ross ’645 discloses the claimed elements “arranged as in the
`
`claim.” See Net MoneyIN, 545 F.3d at 1369.
`
`Moreover, Ross ’645’s disclosure of about 5-95% active ingredient is
`
`insufficient to anticipate the ’159 claims because a prior art reference’s disclosure
`
`of a broad range encompassing the claimed range does not anticipate the narrower
`
`claimed range if the reference does not “describe[] the claimed range with
`
`sufficient specificity.” Atofina, 441 F.3d at 999; see also Kennametal, Inc. v.
`
`Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed. Cir. 2015) (holding that
`
`generic disclosures only anticipate a later claimed species “if a person of skill in
`
`the art, reading the reference, would ‘at once envisage’ the claimed arrangement or
`
`combination”). “The question of ‘sufficient specificity’ is similar to that of
`
`‘clearly envisaging’ a species from a generic teaching.” MPEP § 2131.02.
`
`In Atofina, the Federal Circuit found that the prior art’s disclosure of a
`
`temperature range of 100 to 500˚C failed to describe with sufficient specificity, and
`
`therefore did not anticipate, a claimed range of 330 to 450˚C. 441 F.3d at 999.
`
`Similarly, the Board has denied institution of anticipation challenges where a prior
`
`art reference disclosed a broad range but did not sufficiently specify narrower
`
`claimed amounts. See Mylan Pharm. Inc. v. Boehringer Ingelheim Int’l GmbH,
`
`No. IPR2016-01566, 2017 WL 506739, at *3-4 (P.T.A.B. Feb. 3, 2017) (prior art
`
`dosage range of 1-1000 mg, with preferred range of 1-100 mg, did not anticipate
`
`15
`
`

`

`
`
`
`
`
`
`IPR2018-00390
`Patent Owner’s Preliminary Response
`
`
`claimed amounts of 2.5 mg or 5 mg); Complex Innovations, LLC v. Astrazeneca
`
`AB, No. IPR2017-00631, 2017 WL 3142064, at *4 (P.T.A.B. July 24, 2017)
`
`(“Astrazeneca”) (prior art concentration range of 0.01% to 4% w/w, with preferred
`
`range of 0.1-0.2% w/w, did not anticipate 0.3% w/w concentration).
`
`Petitioner cannot credibly argue