`
`IPR2021-00326
`U.S. Patent 9,856,287
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`______________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________________
`
`LUPIN, LTD. AND LUPIN PHARMACEUTICALS, INC.,
`Petitioners
`
`v.
`AMGEN INC.,
`Patent Owner
`______________________
`Case IPR2021-00326
`Patent 9,856,287
`______________________
`
`
`
`PATENT OWNERS’ PRELIMINARY RESPONSE
`UNDER 37 C.F.R. §42.107
`
`
`
`
`
`
`
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`
`
`

`

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`IPR2021-00326
`U.S. Patent 9,856,287
`
`LIST OF EXHIBITS1
`
`
` EX2001-EX2003, EX2005-EX2007 and EX2013-EX2015 are included for
`
`comparison purposes to show overlap between proceedings and/or availability of
`
`information to the Petitioners. They are not submitted as substantive evidence.
`
`i
`
`
`
` 1
`
`Exhibit
`EX2001
`
`EX2002
`
`EX2003
`
`EX2004
`
`EX2005
`
`EX2006
`
`EX2007
`
`EX2008
`
`EX2009
`
`EX2010
`
`EX2011
`
`Description
`Excerpt of Fresenius Kabi USA, LLC v. Amgen, Inc., IPR2019-
`00971, Pap. 8 (POPR) (July 17, 2019)
`Fresenius Kabi USA, LLC v. Amgen, Inc., IPR2019-00971, Docket
`Sheet
`Excerpt of Adello Biologics, LLC v. Amgen Inc., PGR2019-00001,
`Pap. 3 (Petition) (Oct. 1, 2018)
`Expert Declaration of Richard C. Page, PhD. in Support of Patent
`Owners’ Response (PGR2019-00001) (July 26, 2019)
`Excerpt of Adello Biologics, LLC v. Amgen Inc., PGR2019-00001,
`Pap. 19 (POR) (July 26, 2019)
`Excerpt of Fresenius Kabi USA, LLC v. Amgen, Inc., IPR2019-
`00971, Pap. 3 (Petition) (Apr. 14, 2019)
`Excerpt of Fresenius Kabi USA, LLC v. Amgen, Inc., IPR2020-
`00314, Pap. 4 (Petition) (Dec. 20, 2019)
`Lupin Plans to File Pegilfrastim Biosimilar Drug in Q4FY20 in
`US, available at
`http://www.pharmabiz.com/NewsDetails.aspx?aid=118753&sid=2
`(October 14, 2019)
`Lupin to Launch Etanercept and Pegfilgrastim Biosimilars in the
`US, available at https://gabionline.net/Biosimilars/News/Lupin-to-
`launch-etanercept-and-pegfilgrastim-biosimilars-in-the-US%20
`(Nov. 29, 2019)
`Vallejo, et. al., “Strategies for the Recovery of Active Proteins
`Through Refolding of Bacterial Inclusion Body Proteins,”
`Microbial Cell Factories, Vol 3:11 (2004)
`Lupin Annual Report 2019-2020, available at
`https://lupin.com/pdf/annual-report/2020/lupin-annual-report-2019-
`20-high-res.pdf (March 30, 2020)
`
`
`

`

`
`
`Exhibit
`EX2012
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`EX2013
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`EX2014
`
`EX2015
`
`EX2016
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`
`
`
`IPR2021-00326
`U.S. Patent 9,856,287
`
`Description
`Lupin Corporate Presentation by Vinita Gupta (CEO) at J.P.
`Morgan Healthcare Conference, available at
`https://www.lupin.com/pdf/presentation/2019/lupin-corporate-
`presentation-JPMHC-2018.pdf (Jan. 9, 2018)
`Excerpt of Adello Biologics, LLC v. Amgen Inc., PGR2019-00001,
`Pap. 8 (POPR) (Jan. 23, 2019)
`Adello Biologics, LLC v. Amgen Inc., PGR2019-00001, Docket
`Sheet
`Excerpt of Fresenius Kabi USA, LLC v. Amgen, Inc., IPR2020-
`00314, Pap. 13 (POPR) (Mar. 30, 2020)
`Declaration of Sayem Osman
`
`
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`ii
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`
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`TABLE OF CONTENTS
`
`
`
`
`IPR2021-00326
`U.S. Patent 9,856,287
`
`
`I.
`II.
`
`2.
`
`3.
`
`Page
`Introduction .................................................................................................... 1
`The Challenged Claims Of The ’287 Are Directed To A Novel
`Invention ......................................................................................................... 5
`III. The Board Should Exercise Its Discretion Under §314(a) And
`Deny Institution ............................................................................................. 6
`A.
`The General Plastic Factors Support Denial Of Institution ............ 8
`1.
`Factor 1: Whether Petitioner Previously Filed A
`Petition Directed To The Same Claims Of The Same
`Patent .......................................................................................... 8
`Factor 2: Whether At The Time Of Filing Of The
`First Petition The Petitioner Knew Of The Prior Art
`Asserted In The Later Petition Or Should Have
`Known About It ....................................................................... 12
`Factor 3: Whether At The Time Of Filing Of The
`Later Petition The Petitioner Already Received The
`Patent Owner’s Preliminary Response To The First
`Petition Or Received The Board’s Decision On
`Whether To Institute Review In The First Petition ............. 14
`Factor 4: The Length Of Time That Elapsed Between
`The Time The Petitioner Learned Of The Prior Art
`Asserted In The Later Petition And The Filing Of The
`Later Petition ........................................................................... 22
`Factor 5: Whether The Petitioner Provides Adequate
`Explanation For The Time Elapsed Between The
`Filings Of Multiple Petitions Directed To The Same
`Claims Of The Same Patent ................................................... 23
`Factors 6 and 7: Board’s Considerations Of Finite
`Resources/One-Year Time Line ............................................ 27
`IV. The Board Should Exercise Its Discretion Under §325(d) And
`Deny Institution ........................................................................................... 28
`
`4.
`
`5.
`
`6.
`
`iii
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`

`

`
`V.
`
`B.
`
`C.
`
`Petitioner’s Construction of “Calculated” Is Incorrect (Dependent
`Claims 8, 9, 14, 15, 23, 24, 25, And 30) ...................................................... 36
`VI. The Petition Failed To Establish Anticipation Or Obviousness Of
`Any Challenged Claim ................................................................................ 38
`A.
`Petitioners Failed To Show That Claims 1-4, 7-19, And 22-
`30 Are Anticipated By Vallejo (“Ground 1”) ................................. 39
`1.
`Petitioners Failed To Show Vallejo Teaches The
`Limitation “Thiol-Pair Buffer Strength To Maintain
`The Solubility Of The Preparation/Solution” ...................... 39
`Petitioners Improperly Mix And Match Disclosures
`From Different Embodiments And Fail To Explain
`How The Disclosures In Vallejo Teach The Claim
`Elements ................................................................................... 41
`Petitioners Failed To Present Any Argument Of “Is
`Calculated” Under The Proper Construction (Claims
`8-9, 14-15, 23-25, and 30) ........................................................ 43
`Petitioners Failed To Establish That Claims 1-4, 8-19, and
`23-30 Are Anticipated By Schlegl (“Ground 2”) ............................ 44
`1.
`Petitioners Failed To Address The System In Which
`Schlegl’s Model Protein Is Expressed ................................... 44
`Petitioners Failed To Address The Presence Of DTT
`In Calculating The Thiol-Pair Ratio and Thiol-Pair
`Buffer Strength ........................................................................ 45
`Petitioners Failed To Address The Plural Proteins
`Limitation ................................................................................ 46
`Petitioners Failed To Establish Schlegl Teaches
`“Maintain[ing] The Solubility Of The Preparation
`[Or Solution]” .......................................................................... 48
`Petitioners Failed To Present Any Argument Under
`The Correct Construction Of “Is Calculated” ..................... 49
`Petitioners’ Obviousness Grounds Are Unclear, Confusing,
`and Legally Insufficient (Grounds 3-6) ........................................... 49
`1.
`Petitioners Failed To Clearly Identify The Challenged
`Grounds .................................................................................... 50
`
`
`
`
`IPR2021-00326
`U.S. Patent 9,856,287
`
`2.
`
`3.
`
`2.
`
`3.
`
`4.
`
`5.
`
`iv
`
`

`

`
`
`2.
`
`3.
`
`Petitioners Failed To Provide Sufficient Analysis Of
`The Motivation To Combine For Grounds 3-6 .................... 55
`Petitioners Failed To Sufficiently Articulate A
`Reasonable Expectation Of Success For Grounds 3-6 ........ 61
`VII. Conclusion .................................................................................................... 65
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`IPR2021-00326
`U.S. Patent 9,856,287
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`v
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`IPR2021-00326
`U.S. Patent 9,856,287
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`
`CASES
`10X Genomics, Inc. v. Bio-Rad Labs., Inc.,
`IPR2018-00301, Pap. 18 (June 15, 2018) ........................................................... 64
`Adidas AG v. Nike, Inc.,
`IPR2016-00920, Pap. 6 (Oct. 20, 2016) ................................................. 46, 49, 55
`ADT LLC v. Applied Capital, Inc.,
`IPR2017-01825, Pap. 7 (Jan. 24, 2018) .............................................................. 55
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Gerate
`GmbH,
`IPR2019-01469, Pap. 6 (Feb. 13, 2020) ................................................. 29, 30, 31
`Am. Honda Motor Co. v. Intellectual Ventures II LLC,
`IPR2018-00347, Pap. 10 (June 27, 2018) ........................................................... 16
`Amgen, Inc. v. Iancu,
`No. 19-2171, Dkt. 49 (Fed. Cir. Mar. 24, 2020) ................................................. 57
`Apple, Inc. v. ContentGuard Holdings, Inc.,
`IPR2015-00358, Pap. 9 (July 2, 2015) ............................................................... 59
`Becton, Dickinson and Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Pap. 8 (Dec. 15, 2017) ............................................................. 29
`Biocon Pharma Ltd. v. Novartis Pharms. Corp.,
`IPR2020-01263, Pap. 12 (Feb. 16, 2021) ........................................................... 31
`Chevron Oronite Co. v. Infieum USA LP,
`IPR2018-00923, Pap. 9 (Nov. 7, 2018) .............................................................. 38
`Cisco Sys, Inc. v. C-Cation Techs., LLC,
`IPR2014-00454, Pap. 12 (Aug, 29, 2014) .......................................................... 56
`Clim-A-Tech Indus., Inc. v. Ebert,
`IPR2017-01863, Pap. 13 (Feb. 12, 2018) ........................................................... 49
`
`vi
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`

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`IPR2021-00326
`U.S. Patent 9,856,287
`
`
`Conopco, Inc. v. Procter & Gamble Co.,
`IPR2014-00506, Pap. 17 (July 7, 2014) ............................................................. 34
`Crown Operations Int’l, Ltd. v. Solutia Inc.,
`289 F.3d 1367 (Fed. Cir. 2002) .......................................................................... 39
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016) .......................................................................................... 6
`Deeper, UAB v. Vexilar, Inc.,
`IPR2018-01310, Pap. 7 (Jan. 24, 2019) .............................................................. 38
`Dep’t of Justice v. EnvisionIt, LLC,
`IPR2017-00186, Pap. 8 (May 3, 2017) ............................................................... 50
`Dominion Dealer Sols., LLC v. Autoalert, Inc.,
`IPR2013-00225, Pap. 15 (Oct. 10, 2013) ........................................................... 55
`EIK Engineering SDN. BHD. v. Wilco Marsh Buggies & Draglines,
`Inc.,
`IPR2020-00344, Pap. 7 (June 23, 2020) ....................................................... 54, 59
`Endo Pharm. Inc. v. Depomed, Inc.,
`IPR2014-00653, Pap. 12 (Sept. 29, 2014) .......................................................... 37
`Energysource Minerals, LLC v. Terralithium, LLC,
`IPR2019-01601, Pap. 9 (Mar. 17, 2020) ...................................................... 40, 43
`Everstar Merchandise Co. v. Willis Elec. Co.,
`IPR2019-01484, Pap. 7 (Feb. 20, 2020) ............................................................. 38
`Fluidmaster, Inc. v. Danco, Inc.,
`IPR2017-00770, Pap. 13 (July 28, 2017) ........................................................... 40
`Fresenius Kabi USA, LLC v. Amgen, Inc.,
`IPR2019-00971, Pap. 13 (Oct. 16, 2019) ....................................................passim
`Fresenius Kabi USA, LLC v. Amgen Inc.,
`IPR2019-01183, Pap. 10 (Dec. 10, 2019) ........................................................... 20
`
`vii
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`IPR2021-00326
`U.S. Patent 9,856,287
`
`
`Gen. Plastic Indus. Co. v. Canon Kabushiki Kaisha,
`IPR2016-01357, Pap. 19 (Sept. 6, 2017) .................................................. 7, 14, 21
`Healthcare Logistics, Inc. v. Kit Check, Inc.,
`IPR2019-00385, Pap. 7 (June 3, 2019) ............................................................... 55
`Hengdian Grp. Dmegc Magnetics Co. v. Hitachi Metals, Ltd.,
`IPR2017-01313, Pap. 7 (Nov. 6, 2017) .............................................................. 32
`Hospira, Inc. v. Genentech, Inc.,
`IPR2017-00739, Pap. 16 (July 27, 2017) ........................................................... 28
`Instrumentation Lab. Co. v. Hemosonics, LLC,
`IPR2018-00264, Pap. 8 (May 10, 2018) ............................................................. 16
`Intel Corp. v. Godo Kaisha IP Bridge 1,
`IPR2018-00753, Pap. 11 (Oct. 9, 2018) ............................................................. 28
`Intel Corp. v. Inst. of Microelectronics, Chinese Academy of Scis.,
`IPR2019-00834, Pap. 11 (Oct. 4, 2019) ....................................................... 14, 15
`Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd.,
`821 F.3d 1359 (Fed. Cir. 2016) .......................................................................... 61
`Invue Sec. Prods., Inc. v. Mobile Tech., Inc.,
`IPR2019-00078, Pap. 7 (May 1, 2019) ............................................................... 53
`InVue Sec. Prods. Inc. v. Mobile Tech, Inc.,
`PGR2019-00019, Pap. 7 (May 29, 2019) ........................................................... 53
`Ivantis, Inc. v. Glaukos Corp.,
`IPR2019-00972, Pap. 7 (Oct. 10, 2019) ....................................................... 13, 27
`John Crane, Inc. v. Finalrod IP, LLC,
`IPR2016-01827, Pap. 6 (Jan. 31, 2017) ......................................43, 50, 55, 57, 58
`Johns Manville Corp. v. Knauf Insulation, Inc.,
`IPR2018-00827, Pap. 9 (Oct. 16, 2018) ............................................................. 60
`Juniper Networks, Inc. v. Parity Networks, LLC,
`IPR2018-01642, Pap. 11 (Apr. 10, 2019) ..................................................... 13, 21
`
`viii
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`IPR2021-00326
`U.S. Patent 9,856,287
`
`
`LG Elecs., Inc. v. Bell N. Rsch., LLC,
`IPR2020-00319, Pap. 15 (June 23, 2020) ........................................................... 10
`Lowe’s, Cos., Inc. v. Nichia Corp.,
`IPR2017-02011, Pap. 13 (Mar. 12, 2018) .......................................................... 27
`In re Magnum Oil Tools, Int’l. Ltd.,
`829 F.3d 1364 (Fed. Cir. 2016) .......................................................................... 49
`Microsoft Corp. v. Biscotti, Inc.,
`878 F.3d 1052 (Fed. Cir. 2017) .......................................................................... 41
`Net MoneyIN, Inc. v. VeriSign, Inc.,
`545 F.3d 1359 (Fed. Cir. 2008) .......................................................................... 41
`NetApp Inc. v. Crossroads Sys., Inc.,
`IPR2015-00777, Pap. 12 (Sept. 3, 2015) ............................................................ 34
`NetApp Inc. v. Realtime Data LLC,
`IPR2017-01660, Pap. 17 (Jan. 25, 2018) ............................................................ 15
`Nichia Corp. v. Document Sec. Sys., Inc.,
`IPR2018-01167, Pap. 10 (Nov. 30, 2018) .......................................................... 11
`Nichia Corp. v. Document Sec. Sys., Inc.,
`IPR2019-00398, Pap. 10, 20-21 (Apr. 15, 2019) ............................................... 15
`Nintendo Co. v. Genuine Enabling Tech LLC,
`IPR2018-00543, Pap. 7 (Aug. 6, 2018) .............................................................. 61
`OPEC Engineering Co. v. Berkenhoff GmbH,
`IPR2019-01090, Pap. 11 (Dec. 9, 2019) ............................................................. 60
`Pfizer Inc v. Chugai Pharm. Co.,
`812 F. App’x 979 (Fed. Cir. 2020) ..................................................................... 26
`R.J. Reynolds Vapor Co. v. Fontem Holdings 1 B.V.,
`IPR2017-01319, Pap. 7 (Nov. 8, 2017) .............................................................. 25
`R.J. Reynolds Vapor Co. v. Fontem Holdings 1 B.V.,
`IPR2017-01642, Pap. 10 (Jan. 16, 2018), Pap. 10 (Jan. 16, 2018)..................... 31
`
`ix
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`IPR2021-00326
`U.S. Patent 9,856,287
`
`
`Regeneron Pharms., Inc. v. Kymab Ltd.,
`IPR2020-00389, Pap. 7 (May 26, 2020) ............................................................. 35
`Samsung Elecs. Co. v. ELM 3DS Innovations, LLC,
`IPR2017-01305, Pap. 11 (Oct. 17, 2017) ............................................... 10, 11, 15
`Samsung Elecs. Co. v. Neodron Ltd.,
`IPR2020-00334, Pap. 11 (July 10, 2020) ........................................................... 35
`Sandoz, Inc. v. Genentech, Inc.,
`IPR2017-02036, Pap. 13 (Mar. 4, 2018) ............................................................ 32
`SAS Inst., Inc. v. Iancu,
`138 S. Ct. 1348 (2018) .......................................................................................... 5
`Scanstrut, Inc. v. Nat’l Prods., Inc.,
`IPR2020-01542, Pap. 7 (Mar. 16, 2021) ...................................................... 54, 57
`Shenzhen Silver Star Intelligent Tech. Co. v. iRobot Corp.,
`IPR2018-00897, Pap. 9 (Oct. 1, 2018) ................................................... 13, 21, 27
`In re Stepan Co.,
`868 F.3d 1342 (Fed. Cir. 2017) .......................................................................... 64
`SynQor, Inc. v. Artesyn Techs., Inc.,
`709 F.3d 1365 (Fed. Cir. 2013) .......................................................................... 41
`Teoxane S.A. v. Allergan, PLC,
`IPR2017-01906, Pap. 15 (Mar. 9, 2018) ............................................................ 49
`Unified Patents, Inc. v. Velocity Patent LLC,
`IPR2017-01723, Pap. 10 (Jan. 19, 2018) ............................................................ 32
`United Fire Prot. Corp. v. Engineered Corrosion Soln’s, LLC,
`IPR2018-00991, Pap. 10 (Nov. 15, 2018) .................................................... 11, 14
`Valve Corp. v. Elec. Scripting Prods., Inc.,
`IPR2019-00062, Pap. 11 (Apr. 2, 2019) ............................................. 9, 13, 15, 21
`West Pharm. Servs., Inc. v. Sanofi-Aventis Deutschland GmbH,
`IPR2018-01162, Pap. 7 (Dec. 6, 2018) ............................................................... 33
`
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`IPR2021-00326
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`
`Xactwear Sols., Inc. v. Eagle View Techs., Inc.,
`IPR2017-00034, Pap. 9 (Apr. 13, 2017) ............................................................. 24
`Zetec, Inc. v. Westinghouse Elec. Co.,
`IPR2014-00384, Pap. 10 (Jul. 23, 2014) ............................................................ 53
`ZTE (USA) Inc. v. Fundamental Innovation Sys. Int’l LLC,
`IPR2018-01076, Pap. 14 (Dec. 3, 2018) ............................................................ 15
`STATUTES
`35 U.S.C. § 314 .................................................................................................passim
`35 U.S.C. § 325(d) ............................................................................................passim
`REGULATIONS
`37 C.F.R. § 42.107 ..................................................................................................... 1
`37 C.F.R. § 42.108(c) ............................................................................................. 2, 3
`37 C.F.R. § 42.120 ..................................................................................................... 1
`OTHER AUTHORITIES
`SAS Q&As, D3, at p. 8 (USPTO June 5, 2018), available at
`https://www.uspto.gov/sites/default/files/documents/
`sas_qas_20180605.pdf ........................................................................................ 38
`
`xi
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`

`

`Pursuant to 37 C.F.R. §42.107,2 Patent Owner Amgen Inc. (“Patent Owner”)
`
`
`
`IPR2021-00326
`U.S. Patent 9,856,287
`
`
`
`submits this Preliminary Response to the above-captioned Petition for Inter Partes
`
`Review (“Petition” or “Pet.” Pap. 1) of U.S. Patent No. 9,856,287 (the “’287
`
`patent”), which is the fourth post-grant challenge filed against the ’287 patent.
`
`The present Petition should be denied in its entirety: pursuant to the Board’s
`
`discretion under §314 and/or §325; for Petitioner’s failure to clearly identify its
`
`grounds and obviousness combinations; and for Petitioners’ failure to show a
`
`reasonable likelihood of prevailing on any asserted ground. Institution would not
`
`be in the interests of justice or an efficient use of the Board’s limited time and
`
`resources.
`
`I.
`
`Introduction
`Petitioners’ submission failed to provide the basic evidence required to
`
`institute inter partes review. If the Board nonetheless institutes trial on the
`
`Challenged Claims,3 Amgen will address in detail in its §42.120 Response the
`
`numerous substantive errors and shortcomings in the Petitioners. Here, however,
`
`
`
` 2
`
` All emphasis/annotations added, and all statutory and regulatory citations are to
`
`35 U.S.C. or 37 C.F.R., as the context indicates, unless otherwise stated.
`
`3 Claims 1-30 of the ’287 patent.
`
`1
`
`

`

`
`in this optional preliminary filing subject to a different standard, Amgen addresses
`
`
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`IPR2021-00326
`U.S. Patent 9,856,287
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`only a subset of the Petition’s procedural and substantive shortcomings. Because
`
`of these independent threshold failures, institution of the Petition should be denied.
`
`First, this is the fourth ’287 petition, and institution should be denied under
`
`§314(a). See §III. The current Petition is a quintessential example of improper
`
`road-mapping based on multiple prior proceedings and filings. Petitioners’
`
`assertion that there is “not complete overlap” of challenged claims with the earlier
`
`IPRs fails to acknowledge the complete overlap of the challenged claims with the
`
`earlier PGR. Petitioners offer no meaningful explanation for why they sat by,
`
`clearly monitoring these earlier proceedings in detail before piecing together their
`
`own IPR from snippets of those prior attempts, other than to gain the advantage of
`
`seeing what Patent Owner’s responses would be and how those prior trial runs
`
`played out before the Board.4 The Petition reuses the prior art and recycles—often
`
`verbatim—the arguments presented in those earlier petitions (filed beginning some
`
`
`
` 4
`
` Petitioners’ only attempted explanation relates to standing to appeal based on the
`
`timing of their pegfilgrastim biosimilar. Petitioners’ timing assertions are
`
`contradicted by their own announcements. And, the standing “excuse” is purely
`
`strategic, and thus irrelevant.
`
`2
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`

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`27 months before the present Petition), while improperly leveraging the earlier
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`
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`IPR2021-00326
`U.S. Patent 9,856,287
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`POPRs, POR, and Institution Decision materials as a road-map, all as Petitioners
`
`attempt to address and overcome perceived shortcomings identified in the earlier
`
`papers. The Petition’s content belies Petitioners’ assertion that it did not tailor its
`
`Petition to previously-filed materials.
`
`Second, the present Petition should be denied institution under §325(d).
`
`Although Petitioners assert that “the same or substantially the same art or
`
`arguments were not presented to the Office,” in fact, the identical primary Schlegl
`
`reference and secondary Hevehan reference were specifically overcome during the
`
`’287’s original prosecution. And the other primary reference, Vallejo, is similar to
`
`another Vallejo publication that was in front of the Examiner during prosecution.
`
`Third, Petitioners’ own arguments and evidence confirm they cannot make a
`
`prima facie showing that there is a reasonable likelihood that even one Challenged
`
`Claim is unpatentable. See, e.g., §314; §42.108(c); §V. For example:
`
`•
`
`It is impossible to discern the actual Grounds asserted in the Petition:
`
`Petitioners’ argument headings differ from the arguments below them,
`
`which in turn differ further from the Grounds set forth in the chart on
`
`Petition page 11. Petitioners identify as many as fourteen different Grounds,
`
`3
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`IPR2021-00326
`U.S. Patent 9,856,287
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`but then style them as Grounds “1-6.”5 And certain of those grounds purport
`
`to challenge claims for which no argument is presented at all.
`
`•
`
`For Grounds “1-6,” Petitioners’ analysis regarding apparent inherency and
`
`obviousness arguments is entirely conclusory and consequently insufficient
`
`to meet their burden. With respect to Grounds 4-6, Petitioners fail to explain
`
`how and why the base reference would be modified, and why a POSA would
`
`have had a reasonable expectation of success in doing so. For some
`
`Grounds, Petitioners’ analysis of basic requirements, e.g., reasonable
`
`expectation of success, is missing entirely. And, even when Petitioners
`
`present a single-sentence conclusory assertion purportedly directed to
`
`motivation to combine or reasonable expectation of success, Petitioners
`
`blithely copy their arguments verbatim across base references, ignoring the
`
`differences between those underlying references—and confirming
`
`
`
` 5
`
` Amgen’s reference herein to “Grounds” followed by a number is intended to
`
`cover all grounds that are identified in the Petition as part of those Grounds,
`
`whether in the table of contents, argument headers, chart listing the grounds, or in
`
`the body of the petition itself.
`
`4
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`IPR2021-00326
`U.S. Patent 9,856,287
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`Petitioners made no genuine attempt to address these basic requirements for
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`obviousness on the merits.
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`• With respect to claims 8, 9, 14, 15, 23-25, and 30, Petitioners provide a
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`construction of “is calculated” that is inconsistent with the claim language
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`itself, as well as the doctrine of claim differentiation. And Petitioners fail to
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`take any affirmative position, as required, with respect to whether other
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`claim limitations are limiting.
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`In view of post-SAS all-or-nothing institution, even if, arguendo, the Board
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`were to unearth a Ground with merit buried within Petitioners’ contradictory
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`morass of arguments and combinations reflecting as many as fourteen different
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`grounds, the Board should exercise its discretion here and deny institution.
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`Instituting this proceeding would not be an efficient use of the Board’s limited time
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`and resources given Petitioners’ imprecise, scattershot approach. See, e.g., SAS
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`Inst., Inc. v. Iancu, 138 S. Ct. 1348, 1356 (2018).
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`For the reasons detailed below, the Petition should be denied.
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`II. The Challenged Claims Of The ’287 Are Directed To A Novel Invention
`The ’287 is directed to a novel and efficient protein refolding method based
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`on control of redox conditions with reductant and oxidant (“redox”) reagents.
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`EX1001, 2:62-3:4. The goal of protein refolding is to increase and maximize yield
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`of properly-folded proteins. EX1001, 1:32-38. Desired proteins are recombinantly
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`expressed in non-mammalian culture systems (e.g., bacteria). But, these expressed
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`IPR2021-00326
`U.S. Patent 9,856,287
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`proteins misfold and precipitate in intracellular limited-solubility precipitates
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`known as inclusion bodies. Id., 1:25-30. These inclusion bodies are formed
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`because the intracellular conditions of the bacterial host cell do not favor proper
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`refolding of recombinant proteins. Id., 1:29-31. The host cells are collected and
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`lysed, and then the released inclusion bodies are solubilized in a denaturing
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`solution to linearize the proteins into individual protein chains. Id., 1:43-50.
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`Prior to the ’287 invention, those skilled in the art needed to manipulate a
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`large number of variables—through trial and error—to achieve high yields of
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`properly refolded proteins. Id., 8:47-65. The ’287 inventors addressed the
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`difficulty of identifying acceptable refolding conditions by controlling the
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`concentrations of the reductant and oxidant present in the refolding buffer in a
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`particular manner (e.g., using the interrelationship of thiol-pair ratio (i.e.,
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`[𝑜𝑜𝑜𝑜𝑜𝑜𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟] ) and thiol-pair buffer strength (2[𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜]+[𝑟𝑟𝑟𝑟𝑜𝑜𝑟𝑟𝑟𝑟𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜])) for the
`[𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟]2
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`purpose of properly refolding a recombinantly-expressed protein. Id., 4:52-5:10,
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`6:50-55, 6:63-67.
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`III. The Board Should Exercise Its Discretion Under §314(a) And Deny
`Institution
`Institution of inter partes review is discretionary. See §314(a); Cuozzo
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`Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2140 (2016) (the “decision to deny a
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`petition is a matter committed to the [PTO’s] discretion.”). General Plastic
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`IPR2021-00326
`U.S. Patent 9,856,287
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`enumerated a number of non-exclusive factors that the Board considers in
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`exercising discretion on instituting inter partes review, especially as to “follow-on”
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`petitions challenging the same patent as challenged previously in an IPR, PGR, or
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`CBM. Gen. Plastic Indus. Co. v. Canon Kabushiki Kaisha, IPR2016-01357, Pap.
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`19 (Sept. 6, 2017) (precedential as to § II.B.4.i) (“General Plastic”).
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`The present petition—the fourth post-grant challenge filed against the
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`’287—attempts to improperly leverage the three earlier petitions (and associated
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`expert declarations) challenging this same patent, three POPRs, two Board
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`Institution Decisions, and a POR. It recycles the art and rehashes (often verbatim)
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`the arguments presented in those earlier petitions (filed beginning more than two
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`years before this Petition), while using the earlier POPRs, POR, and Institution
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`Decisions as a road-map in attempting to address perceived shortcomings
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`identified in the earlier papers. The first ’287 post-grant challenge was filed on
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`October 1, 2018 (see EX2003, 20), and the most recent terminated on June 19,
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`2020 (see Pet.3). As discussed below, the Board should exercise its discretion
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`under §314(a) to deny this Petition.
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`IPR2021-00326
`U.S. Patent 9,856,287
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`A. The General Plastic Factors Support Denial Of Institution
`Factor 1: Whether Petitioner Previously Filed A Petition
`1.
`Directed To The Same Claims Of The Same Patent
`While not a party to the earlier Adello PGR (PGR2019-00001) or Fresenius
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`IPRs (IPR2019-00971 and IPR2020-00314), Petitioners—well aware of those prior
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`proceedings—filed a Petition aggressively recycling earlier Grounds, repeating
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`Ground 1 (anticipation by Vallejo) from the PGR and IPRs, repeating Ground 2
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`(anticipation by Schlegl)6 and Ground 3 (obviousness based on Vallejo in view of
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`Hevehan)7 from the PGR, and otherwise presenting Grounds reflecting only minor
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` The PGR petitioners relied on Vallejo in view of Hevehan for claims 5-6, and 20-
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`21, and asserted anticipation of Vallejo for claims 1-4, 7-19, and 22-30. EX2003,
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`12. Similarly, the PGR petitioners relied on Schlegl and Vallejo for claims 7 and
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`22, and asserted anticipation by Schlegl for claims 1-4, 8-19, and 23-30. EX2003,
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`12.
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`7 While the PGR petition’s ground of Vellejo/Hevehan covered only claims 5-6
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`and 20-21 (EX2003, 12), and this Petition’s Vallejo/Hevehan Ground purports to
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`cover claims 1-30 (see Pet.11), the present Petitioners actually invoke Hevehan
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`only in connection with a subset of the claims. See also infra, 51-52, 56-57.
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`permutations on the previously-presented art. Pet.11; EX2003, 12.8 For example,
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`IPR2021-00326
`U.S. Patent 9,856,287
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`the earlier IPRs presented, for claims 8-9, 14-15, 23-25, and 30, the combination
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`of, e.g., Vallejo, Ruddon, Clark, and Schafer or Gilbert (EX2006, 14), while the
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`current Petition purports to present Vallejo and Ruddon and/or Schafer for those
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`same claims (Pet.iii).
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`Petitioners assert this factor weighs “heavily against” denying institution
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`because Petitioners are unrelated to the earlier petitioners and there is “not
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`complete overlap between the challenged claims in this petition and the Fresenius
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`IPRs.” Pet.7-8. Petitioners are wrong.
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` Petitioners also rely on the “knowledge in the art” for certain obviousness
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`grounds in an apparent attempt to hide other secondary references that overlap with
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`those in the prior PGR and IPRs. See, e.g., Pet.52, 57. Those grounds improperly
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`incorporate by reference discussion in the expert declaration (see, e.g., Pet.57
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`citation to EX1002 ¶¶151-152 (citing EX1002 §V.A.5)). Section V.A.5 of the
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`expert declaration, in turn, cites not only to Ruddon and Schafer, but also to Gilbert
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`(EX1030) and Clark 1998 (EX1018), which were secondary references in the
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`earlier IPRs (see EX2006, 6, 14 (where Gilbert appeared as IPR2019-00971
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`EX1014 and Clark 1998 as IPR2019-00971 EX1007)).
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`First, there is complete overlap between the Challenged Claims here and in
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`IPR2