`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________
`TRANSGENE AND BIOINVENT INTERNATIONAL AB
`
`Petitioners,
`
`v.
`
`REPLIMUNE LIMITED
`
`Patent Owner.
`
`Case No. PGR2022-00014
`
`Patent No. 10,947,513
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`
`
`
`

`

`
`TABLE OF CONTENTS
`
`
`PGR2022-00014
`Patent No. 10,947,513
`
`Page
`
`B.
`
`
`INTRODUCTION .......................................................................................... 1
`I.
`BACKGROUND OF THE INVENTION ...................................................... 3
`II.
`III. THE CHALLENGED CLAIM ....................................................................... 4
`IV. SUMMARY OF RELEVANT PROSECUTION HISTORY ........................ 5
`V.
`THE BOARD SHOULD DISCRETIONARILY DENY
`INSTITUTION UNDER 35 U.S.C. § 325(d) ................................................. 7
`A.
`The Petition Relies on the Same or Substantially the Same Art
`Previously Presented to the Office ....................................................... 9
`1.
`Silvestre was Previously Presented to the Office ...................... 9
`2.
`Du was Previously Presented to the Office ............................. 11
`3.
`Zitvogel and Choi Are Cumulative to Silvestre....................... 12
`Petitioners Fail to Demonstrate that the Office Erred in a
`Manner Material to the Patentability of Claim 13 ............................. 13
`VI. LEVEL OF ORDINARY SKILL IN THE ART .......................................... 16
`VII. CLAIM CONSTRUCTION ......................................................................... 17
`VIII. THE PETITION FAILS TO SHOW THAT CLAIM 13 IS MORE
`LIKELY THAN NOT OBVIOUS UNDER 35 U.S.C. § 103 ...................... 17
`A.
`Standard for Institution of Trial on the Merits ................................... 17
`B.
`Legal Standard for Obviousness ........................................................ 18
`C.
`Silvestre Fails to Render Claim 13 Obvious (Ground 4) ................... 19
`1.
`Petitioners Improperly Rely on an Alleged Common
`Knowledge as a Wholesale Substitute for Evidentiary
`Support ..................................................................................... 19
`Petitioners Have Not Adequately Articulated a
`Motivation to Combine Silvestre and Alleged Common
`Knowledge With a Reasonable Expectation of Success .......... 23
`
`2.
`
`
`
`
`
`-i-
`
`
`
`

`

`
`TABLE OF CONTENTS
`(continued)
`
`PGR2022-00014
`Patent No. 10,947,513
`
`Page
`
`2.
`
`
`
`D.
`
`The Combination of Du, Choi, and Zitvogel Fails to Render
`Claim 13 Obvious (Ground 6) ............................................................ 26
`1.
`Petitioners Improperly Rely On an Alleged Common
`Knowledge As A Wholesale Substitute For Evidentiary
`Support ..................................................................................... 27
`Petitioners Have Not Adequately Articulated a
`Motivation to Combine Du, Choi, Zitvogel, and Alleged
`Common Knowledge With a Reasonable Expectation of
`Success ..................................................................................... 29
`IX. CONCLUSION ............................................................................................. 32
`
`
`
`
`
`-ii-
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`

`

`
`
`TABLE OF AUTHORITIES
`
`PGR2022-00014
`Patent No. 10,947,513
`
`Cases
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Geräte
`GmbH,
`IPR2019-01469, Paper 6 (PTAB Feb. 13, 2020) .........................................passim
`Albany Int’l Corp. v. Kimberly-Clark Worldwide, Inc.,
`PGR2021-00019, Paper 22 (PTAB Jun. 22, 2021) (exercising
`discretion under § 325(d) to deny the Petition) .................................................... 7
`Alliance Indus. Corp. v. Gebo Cermex USA, Inc.,
`IPR2019-01647, Paper 9 . (Mar. 24, 2020) ........................................................ 15
`Arendi S.A.R.L. v. Apple Inc.,
`832 F.3d 1355 (Fed. Cir. 2016) ...................................................................passim
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (PTAB Dec. 15, 2017) ..................................... 7, 11, 13
`Biocon Pharma Ltd. v. Novartis Pharm. Corp.,
`IPR2020-01263, Paper 12, 9 (PTAB Feb. 16, 2021) .......................................... 10
`DyStar Textilfarben GMBH v. C. H. Patrick Co.,
`464 F.3d 1356 (Fed. Cir. 2006) .................................................................... 24, 31
`In re Kahn,
`441 F.3d 977 (Fed. Cir. 2006) ............................................................................ 18
`KSR Int'l Co. v. Teleflex Inc.,
`550 U.S. 538 (2007) ............................................................................................ 18
`Medtronic CoreValve LLC et al v. Speyside Med., LLC,
`IPR2021-00240, Paper 9, 23 (PTAB July 23, 2021) .......................................... 10
`Merial, Inc. v. Intervet Int’l B.V.,
`IPR2018-00919, Paper 11 (PTAB Aug. 21, 2018) ............................................. 14
`Regeneron Pharmaceuticals, Inc. v. Kymab Ltd.,
`IPR2019-01579, Paper 9 (Mar. 20, 2020) .......................................................... 15
`
`
`
`iii
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`

`

`PGR2022-00014
`Patent No. 10,947,513
`
`
`Sony Interactive Entm’t LLC v. Terminal Realty, Inc.,
`IPR2020-00711, Paper 15 (PTAB Oct. 13, 2020) .............................................. 14
`In re Stepan Co.,
`868 F.3d 1342 (Fed. Cir. 2017) .......................................................................... 18
`v. AutoStore Technology AS,
`IPR2021-00412, Paper 9 (PTAB July 21, 2021) .................................................. 8
`Vyripharm Enters., Inc. v. Metrc LLC,
`IPR2021-01015, Paper 7 (PTAB Nov. 23, 2021) ............................. 22, 23, 24, 29
`Statutes
`35 U.S.C. 103 ........................................................................................................... 18
`35 U.S.C. § 103 .................................................................................................... 1, 17
`35 U.S.C. § 103(a) (2012) ........................................................................................ 18
`35 U.S.C. § 323 .......................................................................................................... 1
`35 U.S.C. § 324(a) ............................................................................................... 2, 17
`35 U.S.C. § 325(d) ............................................................................................passim
`Other Authorities
`37 C.F.R. § 42.65(a) ........................................................................................... 22, 29
`37 C.F.R. § 42.107(e) ................................................................................................. 1
`37 C.F.R. § 42.108(c) ............................................................................................... 14
`37 C.F.R. § 42.207 ..................................................................................................... 1
`112 Cong. Rec. S1375 (daily ed. Mar. 8, 2011) ...................................................... 17
`U.S. Patent No. 10,947,513 ...............................................................................passim
`
`
`
`iv
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`

`

`PGR2022-00014
`Patent No. 10,947,513
`
`Exhibit
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`EXHIBIT LIST
`Description
`U.S. Patent No. 10,947,513 (“’513 patent”) Prosecution History
`Excerpt – March 15, 2022 Statutory Disclaimer
`’513 patent Prosecution History Excerpt – January 13, 2021
`Examiner Interview Summary
`’513 patent Prosecution History Excerpt – January 29, 2021
`Applicant Interview Summary
`’513 patent Prosecution History Excerpt – February 1, 2021 Notice
`of allowance
`’513 patent Prosecution History Excerpt – Third Party
`Observations
`
`v
`
`
`
`
`
`

`

`PGR2022-00014
`Patent No. 10,947,513
`
`INTRODUCTION
`
`Pursuant to 35 U.S.C. § 323 and 37 C.F.R. § 42.207, Patent Owner Replimune
`
`
`I.
`
`
`Limited (“Replimune” or “Patent Owner”) files this Preliminary Response to
`
`Petitioners Transgene’s and Bioinvent
`
`International AB’s
`
`(collectively,
`
`“Petitioners”) Petition (Paper No. 1, “Pet.”) for post grant review (“PGR”) of U.S.
`
`Patent No. 10,947,513 (“the ’513 Patent”). The Petition requested post-grant review
`
`of claims 1-8 and 10-26 of the ’513 Patent.
`
`
`
`Patent Owner has disclaimed claims 1-8, 10-12, and 14-26 by way of a
`
`Statutory Disclaimer filed on March 15, 2022. Ex. 2001. Thus, only claim 13
`
`remains at issue in this proceeding,1 which Petitioners allege is unpatentable under
`
`35 U.S.C. § 103 as being obvious in view of Silvestre (Ex. 1002) and the POSITA’s
`
`alleged common knowledge (Ground 4), and obvious in view of the combination of
`
`Du (Ex. 1003), Choi (Ex. 1005), Zitvogel (Ex. 1004) and the POSITA’s alleged
`
`common knowledge (Ground 6). For at least the reasons described below, the Board
`
`should deny Petitioners’ request for PGR.
`
`
`
`First, the Board should deny institution under 35 U.S.C. § 325(d) because
`
`Petitioners’ arguments as to the only remaining claim rely on the same or
`
`
`1 See 37 C.F.R. § 42.107(e) (“No inter partes review will be instituted based on
`
`disclaimed claims.”)
`
`
`
`

`

`
`substantially the same art previously presented to the United States Patent and
`
`PGR2022-00014
`Patent No. 10,947,513
`
`Trademark Office (hereinafter, “the Office”). Both Silvestre (Ground 4) and Du
`
`(Ground 6) were listed in an information disclosure statement (“IDS”) considered
`
`by the Office during prosecution. Moreover, Choi and Zitvogel’s (Ground 6)
`
`teachings are cumulative to the teachings of Silvestre. In their Petition, the
`
`Petitioners ignore their burden to demonstrate that the Office erred in a manner
`
`material to patentability of claim 13, and, thus, the Petition should be denied under
`
`35 U.S.C. § 325(d). Discretion is well exercised when the Office declines to expend
`
`its limited resources re-evaluating the same art or arguments when there has not even
`
`been an assertion that it erred the first time around.
`
`
`
`Second, to the extent the Board declines to exercise discretion to deny
`
`institution based on 35 U.S.C. § 325(d), it should nonetheless deny institution on the
`
`merits, because Petitioners have failed to demonstrate that claim 13 is more likely
`
`than not unpatentable. See 35 U.S.C. § 324(a).
`
`
`
`As explained more fully below, for each of its obviousness grounds asserted
`
`against claim 13 (Ground 4 and Ground 6), Petitioners improperly rely on alleged
`
`common knowledge to supply claim limitations missing from the cited prior art. The
`
`case law is clear that while common knowledge or common sense may be invoked
`
`in an obviousness inquiry, it is typically invoked only to provide a motivation to
`
`combine, and cannot be used as a wholesale substitute for reasoned analysis and
`
`
`
`2
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`

`

`
`evidentiary support when addressing a missing claim limitation from the prior art.
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`PGR2022-00014
`Patent No. 10,947,513
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`Petitioners have violated this well-established understanding of the use of common
`
`knowledge in an obviousness inquiry in an effort to remedy their deficient analysis.
`
`II. BACKGROUND OF THE INVENTION
`
`Viruses have a unique ability to enter cells at high efficiency, and, after
`
`entering the cells, viral genes can be expressed such that the virus can replicate. Ex.
`
`1001 at 1:22-26. The invention of the ’513 Patent relates to a specific type of virus:
`
`oncolytic viruses, which infect and replicate in tumor cells such that the tumor cell
`
`is killed. Ex. 1001 at 9:10-12. This ability of oncolytic viruses to infect and replicate
`
`in tumor cells makes them useful for the treatment of cancer.
`
`
`
`As described in the background of the ’513 Patent, one type of virus that has
`
`found utility in the oncolytic treatment of cancer is the herpes simplex virus
`
`(“HSV”). Id. at 2:9-11. In order for HSV to be utilized in oncolytic treatment, it
`
`must first be disabled such that it is no longer pathogenic but can still enter and kill
`
`tumor cells. Id. at 2:11-14. To achieve this, a number of disabling mutations have
`
`been used, including, for example, disrupting genes encoding ICP34.5, ICP6, and/or
`
`thymidine kinase. Id. at 2:14-24.
`
`
`
`Oncolytic viruses can also be used to deliver a therapeutic gene to treat cancer.
`
`Id. at 2:25-27. As described by the ’513 Patent, for example, an ICP34.5 deleted
`
`HSV virus can also encode a heterologous gene for GM-CSF, which is a pro-
`
`
`
`3
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`

`

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`inflammatory cytokine having multiple functions and is important for the
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`PGR2022-00014
`Patent No. 10,947,513
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`proliferation and maturation of antigen presenting cells that are needed to activate
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`an anti-tumor response. Id. at 2:25-38. Not only can these viruses encode a
`
`heterologous gene for GM-CSF but they also can be engineered to include immune
`
`co-stimulatory pathway activating molecule encoding genes. Id. at 2:49-4:3. By
`
`targeting immune co-stimulatory pathways, the anti-tumor immune response can be
`
`amplified. Id. at 3:12-5:3.
`
`III. THE CHALLENGED CLAIM
`
`Claim 13 is the only challenged claim remaining at issue in this proceeding
`
`(all other challenged claims have been disclaimed). Claim 13 recites:
`
`13. The virus of claim 11, wherein the GM-CSF-encoding gene and the
`CTLA-4 inhibitor encoding gene are inserted into the ICP34.5 encoding
`locus, either by insertion, or partial or complete deletion, in a back to
`back orientation in relation to each other, each under separate
`regulatory control.
`
`Claims 1 and 11 from which claim 13 depends are reproduced below:
`
`1. An oncolytic virus comprising: (i) a heterologous GM-CSF-encoding
`gene; and (ii) a heterologous CTLA-4 inhibitor encoding gene, wherein
`both heterologous genes are inserted into the genome of the virus.
`
`11. The virus of claim 1, which is a herpes simplex virus (HSV).
`
`
`
`4
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`

`

`
`IV. SUMMARY OF RELEVANT PROSECUTION HISTORY
`
`The ’513 Patent was filed as U.S. Application No. 16/068,830 (“the ‘830
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`PGR2022-00014
`Patent No. 10,947,513
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`Application”) on July 9, 2018, as a national stage entry application of
`
`PCT/GB2017/050038 with a PCT filing date of January 9, 2017. Ex. 1001, 1.
`
`Before any Office Action issued, Applicant filed an IDS with the Office on October
`
`16, 2018 that included, among other references, Silvestre and Du (hereinafter,
`
`“October 2018 IDS”). Ex. 1018 at 5.2
`
`
`
`The Examiner thoroughly reviewed the application issuing a number of office
`
`actions and conducting a number of interviews with the Applicant. On December
`
`23, 2020, the Examiner issued a Notice of Allowance with a signed copy of the
`
`October 2018 IDS that included Silvestre and Du. Ex. 1019 at 5. Of note, the
`
`October 2018 IDS includes the Examiner’s signature with a date of August 19, 2019
`
`and acknowledges that the Examiner considered all references. Id. The Examiner
`
`mailed yet another Notice of Allowance on December 29, 2020 (having a corrected
`
`Notice of Allowability), which was accompanied by another copy of the October
`
`
`Silvestre issued from a U.S. National Stage Application of International
`
`2
`
`Application No. PCT/EP2015/066263 (published as WO2016/008976 (“WO
`
`’976”)). Ex. 1002 at Cover. WO ’976 was included in the Oct. 2018 IDS. Ex. 1018
`
`at 5.
`
`
`
`5
`
`

`

`
`2018 IDS, but in this IDS, the Examiner had crossed out all of the listed references.
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`PGR2022-00014
`Patent No. 10,947,513
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`Ex. 1020.
`
`
`
`The Examiner and Applicant had an interview on January 7, 2021 and
`
`discussed the duplicate copy of the October 2018 IDS and the crossed-out
`
`references. Ex. 2002 at 3. As noted in the interview summary provided by the
`
`examiner, the references in the October 2018 IDS were crossed out because they all
`
`have duplicated copies “previously considered by the examiner.” Id. Specifically,
`
`the Examiner stated:
`
`The duplicated IDSs filed on 10/16/2018, 8/19/2019 previous
`[sic] signed and sent to you and a document filed as a Third party
`submitted on 07/30,2019 that were all considered as IDS
`previously. They were all crossed over because they all have
`duplicated copies previously considered by the examiner.
`
`Id.
`
`
`
`The Applicant memorialized this interview in its own interview summary
`
`filed on January 29, 2021. Ex. 2003. Specifically, the Applicant explained that “the
`
`examiner and the undersigned had a telephonic interview with respect to clarification
`
`of consideration of IDS references, given crossing out of the references in the
`
`Corrected Notice of Allowability of December 29, 2020, when the references had
`
`been previously considered. The examiner clarified that such action was taken
`
`
`
`6
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`

`
`because they were duplicated copies of previously considered references.” Id. at
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`PGR2022-00014
`Patent No. 10,947,513
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`1-2 (emphasis added).
`
`
`
`The Examiner issued another Notice of Allowance on February 1, 2021 (Ex.
`
`2004), and the application ultimately issued as the ’513 Patent on March 16, 2021.
`
`V. THE BOARD SHOULD DISCRETIONARILY DENY INSTITUTION
`UNDER 35 U.S.C. § 325(D)
`
`The Board has statutory discretion to deny a PGR when the petition relies on
`
`the same or substantially the same prior art or arguments that were previously
`
`presented to the Office. See 35 U.S.C. § 325(d); see also Albany Int’l Corp. v.
`
`Kimberly-Clark Worldwide, Inc., PGR2021-00019, Paper 22, at 40 (PTAB Jun. 22,
`
`2021) (exercising discretion under § 325(d) to deny the Petition). The precedential
`
`Advanced Bionics decision establishes a two-part framework for the Board’s
`
`determination of whether to exercise discretion under this section. Advanced
`
`Bionics, LLC v. MED-EL Elektromedizinische Geräte GmbH, IPR2019-01469,
`
`Paper 6 at 8-9 (PTAB Feb. 13, 2020) (precedential). This framework considers: (i)
`
`whether the same or substantially the same art or arguments were previously
`
`presented to the Office; and (ii) if either condition is satisfied in the first part,
`
`whether the petitioner has demonstrated that the Office erred in a manner material
`
`to the patentability of the challenged claims. Id.; see also Becton, Dickinson & Co.
`
`
`
`7
`
`

`

`
`v. B. Braun Melsungen AG, IPR2017-01586, Paper 8 at 17-18 (PTAB Dec. 15, 2017)
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`PGR2022-00014
`Patent No. 10,947,513
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`(precedential).
`
`Here, as Petitioners concede, both Silvestre (Ground 4) and Du (Ground 6)
`
`were listed in an IDS early in prosecution. Pet. at 8-9. Petitioners nonetheless
`
`incorrectly state that Silvestre and Du were not considered by the Office despite
`
`several interview summaries in the publicly-available prosecution history clearly
`
`establishing otherwise. And while Petitioners add Choi and Zitvogel to Ground 6,
`
`their teachings are cumulative to the teachings of Silvestre.
`
`Petitioners have also failed to present any persuasive evidence that the Office
`
`materially erred in allowing claim 13, “a required element of Petitioner’s burden to
`
`overcome the Board’s exercise of discretionary denial under § 325(d).” Ocado
`
`Group plc v. AutoStore Technology AS, IPR2021-00412, Paper 9, at 38 (PTAB July
`
`21, 2021) (citing Advanced Bionics, Paper 6, at 8-9 (“If a condition in the first part
`
`of the framework is satisfied and the petitioner fails to make a showing of material
`
`error, the Director generally will exercise discretion not to institute inter partes
`
`review.”)).
`
`Accordingly, as (i) the Silvestre and Du references were considered by the
`
`Examiner in allowing the claims, (ii) Zitvogel and Choi are cumulative to Silvestre,
`
`and (iii) Petitioners have failed to present a showing of material error, the Board
`
`should exercise its discretion to not institute review.
`
`
`
`8
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`

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`PGR2022-00014
`Patent No. 10,947,513
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` The Petition Relies on the Same or Substantially the Same Art
`Previously Presented to the Office
`
`The first determination in the § 325(d) analysis is whether the Office
`
`
`
`
`
`previously considered the same or substantially the same prior art disclosures.
`
`Advanced Bionics at 7.
`
`1. Silvestre was Previously Presented to the Office
`Petitioners rely on Silvestre in Ground 4 as the sole reference (together with
`
`
`
`the POSITA’s alleged common knowledge) for their obviousness challenge. Pet. at
`
`3. Silvestre issued from a U.S. National Stage Application of International
`
`Application No. PCT/EP2015/066263 (published as WO2016/008976 (“WO
`
`’976”)). Ex. 1002 at Cover. WO ’976 was presented to the Office in the October
`
`2018 IDS. Ex. 1018 at 5. On August 22, 2019, the Examiner provided a signed
`
`copy of the IDS with the statement “all references considered …” Ex. 1019 at 5.
`
`Petitioners suggest that the October 2018 IDS was not considered because “a
`
`week later, that IDS was entered again with all of the references crossed off.” Pet.
`
`at 9. But as Applicant explained in a January 29, 2021 interview summary, and as
`
`Petitioners fail to mention to the Board, “the examiner and the undersigned had a
`
`telephonic interview with respect to clarification of consideration of IDS references,
`
`given crossing out of the references in the Corrected Notice of Allowability of
`
`December 29, 2020, when the references had been previously considered. The
`
`
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`9
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`examiner clarified that such action was taken because they were duplicated copies
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`PGR2022-00014
`Patent No. 10,947,513
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`of previously considered references.” Ex. 2003 at 1-2 (emphasis added); see also
`
`Ex. 2002 at 3. The consideration of WO ’976 is clearly reflected on the cover page
`
`of the Challenged Patent:
`
`
`
`Ex. 1001 at 1.
`As explained in Advanced Bionics, “[p]reviously presented art includes art
`
`made of record … such as on an [IDS].” Advanced Bionics, 7-8 (emphasis added);
`
`see also Biocon Pharma Ltd. v. Novartis Pharm. Corp., IPR2020-01263, Paper 12,
`
`9 (PTAB Feb. 16, 2021) (“Thus, we accept that the Examiner considered EP ’072
`
`because it is listed on the IDS and the Examiner signed the IDS with the statement
`
`‘all references considered except where lined through.’”) (emphasis added);
`
`Medtronic CoreValve LLC et al v. Speyside Med., LLC, IPR2021-00240, Paper 9,
`
`
`
`10
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`

`

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`23 (PTAB July 23, 2021) (“Petitioner, however, seems to limit this factor to
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`PGR2022-00014
`Patent No. 10,947,513
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`references that are expressly included in a rejection by the examiner. This factor is
`
`not so limited … [p]reviously presented art includes ... art provided to the Office by
`
`an applicant, such as on an [IDS].”) (emphasis added). Thus, the first part of the
`
`Advanced Bionics framework is satisfied with respect to Silvestre, as Silvestre is the
`
`same art previously presented to, and considered, by the Office.
`
`Despite the clarity around the October 2018 IDS, Petitioners nonetheless
`
`ignore this portion of the prosecution history in their Petition, and instead take the
`
`inaccurate position that Silvestre was not considered by the Examiner, and fail to
`
`address the Becton, Dickinson factors despite being encouraged to do so by the
`
`PTAB. See, e.g., Consolidated Trial Practice Guide at 61-63.
`
`2. Du was Previously Presented to the Office
`Petitioners rely on Du in Ground 6 as one of three references for their
`
`
`
`obviousness challenge. Pet. at 4. Du was previously presented to the Office in the
`
`October 2018 IDS (Ex. 1018 at 5), which the Examiner signed on August 22, 2019
`
`with the statement that “all references [were] considered …” Ex. 1019 at 5. The
`
`submission and consideration of Du is reflected on page 2 of the Challenged Patent:
`
`
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`11
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`PGR2022-00014
`Patent No. 10,947,513
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`
`
`Ex. 1001 at 2.
`
`
`
`Since “[p]reviously presented art includes art made of record … such as on
`
`an [IDS],” Advanced Bionics at 7-8, the first part of the Advanced Bionics
`
`framework is satisfied with respect to Du.
`
`As discussed above, despite the clarity around the October 2018 IDS,
`
`Petitioners nonetheless ignore this portion of the prosecution history in their Petition,
`
`and instead take the inaccurate position that Du was not considered by the Examiner.
`
`3. Zitvogel and Choi Are Cumulative to Silvestre
`In addition to Du, Petitioners rely on Zitvogel and Choi in Ground 6 for their
`
`
`
`obviousness challenge of claim 13. Pet. at 4. With respect to Zitvogel, Petitioners
`
`rely only on the following: “[a]nother aspect involves [HSV] viral mutants with
`
`defects in the function of genes encoding virulence factors such as the ICP34.5 gene
`
`… Representative examples of oncolytic herpes virus include NV1020 … and T-
`
`VEC.” Pet. at 74. Such disclosure is cumulative to Silvestre, which also discloses
`
`
`
`12
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`the use of T-VEC—a genetically modified HSV with defects in the function of genes
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`PGR2022-00014
`Patent No. 10,947,513
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`encoding virulence factors. Id. at 54. And as to Choi, which is not directly applied
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`against claim 13, its disclosure is cumulative to that of Silvestre, as evidenced by the
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`fact that Petitioner has asserted that Silvestre anticipates claims 1 and 11, on which
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`claim 13 depends. See Ground 3. Therefore, the first part of the Advanced Bionics
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`framework is satisfied with respect to Zitvogel and Choi.
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`Petitioners Fail to Demonstrate that the Office Erred in a Manner
`Material to the Patentability of Claim 13
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`
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`Under the Advanced Bionics framework, if a petitioner relies on the same or
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`substantially the same prior art disclosures that were previously presented to, and
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`considered by, the Office, the petitioner must then make a showing of material error
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`by the Examiner. Advanced Bionics at 8; (citing Becton, Dickinson, Paper 8 at 24
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`(discretion appropriate where “petitioner fails to show that the Office erred”)). “An
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`example of a material error may include misapprehending or overlooking specific
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`teachings of the relevant prior art where those teachings impact patentability of the
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`challenged claims.” Id. at 8 n.9. “If reasonable minds can disagree regarding the
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`purported treatment of the art or arguments, it cannot be said that the Office erred in
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`a manner material to patentability.” Id. at 9.
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`Here, Petitioners do not even allege that the Examiner committed any material
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`error (tellingly the phrase “material error” does not appear anywhere in the
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`13
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`Petition).3 The closest Petitioners come to alleging error is by arguing that “[t]he
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`record does not reflect that the Examiner appreciated the teachings of either Silvestre
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`or Du as neither formed the basis for any rejections.” Pet. at 9. But that statement
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`alone is insufficient to carry a petitioner’s burden as to the second part of the
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`Advanced Bionics framework, i.e., explain how the examiner committed a material
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`error. See, e.g., Sony Interactive Entm’t LLC v. Terminal Realty, Inc., IPR2020-
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`00711, Paper 15 at 12 (PTAB Oct. 13, 2020) (Petitioner’s argument that asserted
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`references were not substantively evaluated or applied in a rejection failed to
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`sufficiently identify examiner error).
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`
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`Additionally, claim 13, which indirectly depends from claim 1, adds the
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`limitation that “the GM-CSF-encoding gene and the CTLA-4 inhibitor encoding
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`Advanced Bionics was designated precedential on March 24, 2020, long
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`3
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`before the Petition was filed on December 15, 2021. Petitioners reasonably should
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`have anticipated Patent Owner’s arguments pertaining to the Advanced Bionics
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`framework, particularly when Petitioners’ asserted references are the same or
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`substantially the same references considered during prosecution. Thus, Petitioners
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`cannot show the good cause required if they were to request a reply. See Merial,
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`Inc. v. Intervet Int’l B.V., IPR2018-00919, Paper 11 at 2-3 (PTAB Aug. 21, 2018)
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`(citing 37 C.F.R. § 42.108(c)); see also Consolidated Trial Practice Guide at 61-63.
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`gene are inserted … in a back to back orientation in relation to each other, each
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`under separate regulatory control.” Ex. 1001 at 83:20-25 (emphasis added).
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`Petitioners do not allege that Silvestre, Du, Choi and/or Zitvogel disclose or suggest
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`that limitation either singly or in combination.
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`
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`Instead, Petitioners simply state that “[t]he simplest and most common
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`method to insert two genes to a locus is in a back-to-back orientation under control
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`of separate regulatory elements.” Pet. at 54-55 (Ground 4, claim 13), 74 (Ground 6,
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`claim 13). Petitioners’ expert repeats, almost verbatim, the same unsupported
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`assertion. Ex. 1007 ¶ 230 (“[T]he simplest and most common way to do so is to
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`insert them in a back-to-back orientation under control of separate regulatory
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`elements.”); id. ¶ 319.4 However, expert testimony that merely repeats the
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`arguments in the Petition is given little or no weight as it “adds little to the analysis.”
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`Alliance Indus. Corp. v. Gebo Cermex USA, Inc., IPR2019-01647, Paper 9 at 27.
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`(Mar. 24, 2020); see also Regeneron Pharmaceuticals, Inc. v. Kymab Ltd., IPR2019-
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`01579, Paper 9 at 18 (Mar. 20, 2020) (“[T]he fact that the Declaration of Petitioner’s
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`4 While Petitioners cite Ex. 1078 against claim 13, they do not assert that it
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`discloses inserting two heterologous genes let alone two heterologous genes in a
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`back-to-back orientation in relation to each other, each under separate regulatory
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`control. See Pet. at 54 and 74.
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`15
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`expert was not before the Examiner during prosecution does not itself demonstrate
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`that the Examiner erred.”). Indeed, it is unclear how the Examiner could have erred
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`by not considering Silvestre, Du, Choi and/or Zitvogel in allowing claim 13 when
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`Petitioners do not even allege that the references disclose or suggest the recited claim
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`limitation.5 Accordingly, Petitioners have not shown that the Examiner erred in a
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`manner material to patentability. Advanced Bionics at 9.
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`VI. LEVEL OF ORDINARY SKILL IN THE ART
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`Petitioners assert that a POSITA as of the effective filing date of the ’513
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`Patent “would have had a Ph.D. in molecular biology, or a related field, with
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`expertise in virology (including expertise growing, isolating, and rescuing viruses),
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`immunology, and cancer biology with at least four years of post-Ph.D. experience
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`in those areas.” Pet. at 6.
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`5 To the extent Petitioners assert that the Examiner was somehow not aware of the
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`alleged common knowledge of a POSITA, which Petitioners assert teach that
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`limitation, that argument fails. Examiners “are assumed to have some expertise in
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`interpreting the references and to be familiar from their work with the level of skill
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`in the art and whose duty it is to issue only valid patents.” Ultra–Tex Surfaces, Inc.
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`v. Hill Bros. Chemical Co., 204 F.3d 1360, 1367 (Fed. Cir. 2000).
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`Solely for purposes of this Preliminary Response, Patent Owner does not
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`dispute Petitioners’ definition of a POSITA. Patent Owner reserves the right to
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`present a different definition in the unlikely event that the Board institutes review.
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`VII. CLAIM CONSTRUCTION
`Petitioners offer a construction for the term “oncolytic virus” in claim 1 of the
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`
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`’513 Patent. Specifically, Petitioners assert that “oncolytic virus” should be
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`construed to mean “a virus that infects and replicates in tumor cells, such that the
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`tumor cells are killed.” Pet. at 6.
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`
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`Solely for purposes of this Preliminary Response, Patent Owner does not
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`dispute Petitioners’ construction of the term “oncolytic virus,” although Patent
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`Owner does dispute Petitioners’ characterization that the “specification defines” the
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`term. Pet. at 6. Patent Owner reserves the right to present a different construction
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`in the unlikely event that the Board institutes review.
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`VIII. THE PETITION FAILS TO SHOW THAT CLAIM 13 IS MORE
`LIKELY THAN NOT OBVIOUS UNDER 35 U.S.C. § 103
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`As articulated in 35 U.S.C. § 324(a), “[t]he Director may not authorize a post-
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`Standard for Institution of Trial on the Merits
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`
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`grant review to be instituted unless the Director determines that the information
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`presented in the petition . . . would demonstrate that it is more likely than not that
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`at least 1 of the claims challenged in the petition is unpatentable.” 35 U.S.C.
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`§ 324(a) (emphasis added). This “more likely than not” standard is a “slightly higher
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`threshold” than the “reasonable likelihood of success” standard employed in inter
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`partes review proceedings. 112 Cong. Rec. S1375 (daily ed. Mar. 8, 2011).
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`For the reasons describ