UNITED STATES PATENT AND TRADEMARK OFFICE
`
`———————
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`———————
`
`Regeneron Pharmaceuticals, Inc.,
`Petitioner,
`
`v.
`
`Novartis Pharma AG,
`Novartis Technology LLC,
`Novartis Pharmaceuticals Corporation,
`Patent Owner
`
`———————
`
`Case IPR2020-01317
`U.S. Patent No. 9,220,631
`———————
`PETITIONER’S REPLY REGARDING 35 U.S.C. §§ 314(a), 325(d)
`
`

`

`TABLE OF CONTENTS
`
`ARGUMENT …………………………………………………………….. 2
`
`A.
`
`B.
`
`The Becton Dickinson Factors Favor Institution ................................... 2 
`1.
`Becton Dickinson Factors (a)-(c) ................................................ 2
`2.
`Becton Dickinson Factors (d)-(e) ................................................ 7
`3.
`Becton Dickinson Factor (f) and Conclusion re § 325(d) ........... 8
`
`The Fintiv Factors Favor Institution ..................................................... 9 
`1.
`Factor 1: Whether a Stay Was Granted ...................................... 9
`2.
`Factor 3: Investment in the Parallel Proceeding ....................... 11
`3.
`Factor 4: There Will Be No Overlap Between Issues ............... 12
`Factor 2: The ITC and Board Schedules Are as Close in ......... 13
`4.
`Proximity as Practicably Possible
`
`Factors 5, 6 & Conclusion re § 314(a) ...................................... 14
`
`5.
`
`i
`
`

`

`
`
`EXHIBIT LIST
`Description
`Exhibit
`Ex. 1001 U.S. Patent No. 9,220,631 (“the ’631 Patent”)
`
`Ex. 1002 Prosecution File History of U.S. Patent No. 9,220,631
`
`Ex. 1003 Declaration of Horst Koller under 37 C.F.R. § 1.68.
`
`Ex. 1004 Curriculum Vitae of Horst Koller
`
`Ex. 1005 Declaration of James Agalloco under 37 C.F.R. § 1.68.
`
`Ex. 1006 Curriculum Vitae of James Agalloco
`
`Ex. 1007 PCT Patent Publication No. WO 2011/006877 to Sigg et al. (“Sigg”)
`
`Ex. 1008 PCT Patent Publication No. WO 2009/030976 to Boulange et al.
`(“Boulange”)
`
`Ex. 1009 Internet Archive WayBack Machine, March 7, 2011 Record of
`Drugs.com, Macugen Prescribing Information, available at
`https://web.archive.org/web/20110307065238/http://www.drugs.com:
`80/pro/macugen.html (“Macugen® Label”)
`
`Ex. 1010 Certified English Translation of Bruno Reuter and Claudia Petersen.
`“Die Silikonisierung von Spritzen: Trends, Methoden,
`Analyseverfahren,” TechnoPharm 2, Nr. 4 (2012): 238-244.
`(“Reuter”)
`
`Ex. 1011 Bhavnesh D. Shah & Bhupendra G. Prajapati, Pre-Filled Syringes: A
`New Concept, PHARMA BIO WORLD 51 (2009) (“Shah”)
`
`Ex. 1012 Arno Fries, Drug Delivery of Sensitive Biopharmaceuticals With
`Prefilled Syringes, 9(5) DRUG DELIVERY TECH. 22 (2009) (“Fries”)
`
`Ex. 1013 Thomas Schoenknecht, Prefilled Syringes: Why New Developments
`Are Important In Injectable Delivery Today, in PREFILLED SYRINGES
`INNOVATIONS THAT MEET THE GROWING DEMAND (OnDrugDelivery
`2005) (“Schoenknecht”)
`
`
`
`
`ii
`
`

`

`
`
`Description
`Exhibit
`Ex. 1014 U.S. Patent Publication No. 2012/0091026 to Chacornac et al.
`(“Chacornac”)
`
`Ex. 1015 Sandeep Nema & John D. Ludwig, Pharmaceutical Dosage Forms:
`Parenteral Medications, Volume 1: Formulation and Packaging (3rd
`ed. 2010) (“Nema Vol. 1”)
`
`Ex. 1016 Sandeep Nema & John D. Ludwig, Pharmaceutical Dosage Forms:
`Parenteral Medications, Volume 2: Facility Design, Sterilization and
`Processing (3rd ed. 2010) (“Nema Vol. 2”)
`
`Ex. 1017 PCT Patent Publication No. WO 2007/035621 to Scypinski et al.
`(“Scypinski”)
`
`Ex. 1018 U.S. Patent Publication No. 2003/0003014 to Metzner et al.
`(“Metzner”)
`
`Ex. 1019 U.S. Pharmacopeia, USP 789, Particulate Matter in Ophthalmic
`Solutions, USP 34 NF 29 (2011)
`
`Ex. 1020 U.S. Patent Publication No. 2011/276005 to Hioki et al. (“Hioki”)
`
`Ex. 1021 PCT Patent Publication No. WO 2007/149334 to Furfine et al.
`(“Furfine”)
`
`Ex. 1022 Michael W. Stewart et al., Fresh From the Pipeline Aflibercept, 11
`NAT. REV. DRUG DISCOV. 269 (2012) (“Stewart”)
`
`Ex. 1023 U.S. Patent No. 7,060,269 to Baca et al. (“Baca”)
`
`Ex. 1024 Prosecution File History of U.S. Patent No. 7,060,269
`
`Ex. 1025 Lu Liu et al., Silicone Oil Microdroplets and Protein Aggregates in
`Repackaged Bevacizumab and Ranibizumab: Effects of Long-term
`Storage and Product Mishandling, 52(2) INVESTIGATIVE
`OPHTHALMOLOGY & VISUAL SCIENCE 1023 (2011) (“Liu”)
`
`Ex. 1026 U.S. Patent No. 7,404,278 to Wittland et al. (“Wittland”)
`
`
`
`
`iii
`
`

`

`
`
`Description
`Exhibit
`Ex. 1027 U.S. Food and Drug Administration, Lucentis® Highlights of the
`Prescribing Information, (June 2010) (“Lucentis® Label”)
`
`Ex. 1028 International Organization for Standardization, ISO 11040-4 Prefilled
`Syringes – Part 4: Glass Barrels for Injectables (2nd ed. 2007) (“ISO
`11040-4”)
`
`Ex. 1029 PCT Patent Publication No. WO 2008/077155 to Lam et al. (“Lam”)
`
`Ex. 1030 James A. Dixon, et al. "VEGF Trap-Eye for the treatment of
`neovascular age-related macular degeneration." Expert opinion on
`investigational drugs 18.10 (2009): 1573-1580. (“Dixon”)
`
`Ex. 1031 Declaration of Dr. Szilard Kiss under 37 C.F.R. § 1.68.
`
`Ex. 1032 Curriculum Vitae of Dr. Szilard Kiss
`
`Ex. 1033 Declaration of James L. Mullins, Ph.D.
`
`Ex. 1034 Dow Corning® 365 35% Dimethicone NF Emulsion – Frequently
`Asked Questions (2002) (“DC365 FAQ”)
`
`Ex. 1035 European Patent Application No. 12174860 to Novartis AG
`
`Ex. 1036 U.S. Food and Drug Administration, Guidance for Industry: Sterile
`Drug Products Produced by Aseptic Processing—Current Good
`Manufacturing Practice (September 2004)
`
`Ex. 1037 Affidavit of Internet Archive Office Manager
`
`Ex. 1038 Internet Archive WayBack Machine, March 8, 2011 Record of
`Drugs.com, Welcome to Drugs.com, available at
`https://web.archive.org/web/20110308203650/http://www.drugs.com:
`80/
`
`Ex. 1039 Internet Archive WayBack Machine, February 25, 2011 Record of
`Drugs.com, FDA Professional Drug Information, available at
`https://web.archive.org/web/20110225193929/http://www.drugs.com:
`80/pro/
`
`
`
`
`iv
`
`

`

`
`
`Description
`Exhibit
`Ex. 1040 U.S. Food and Drug Administration, Eylea® Highlights of the
`Prescribing Information, (November 2011) (“Eylea label”)
`Ex. 1041 U.S. Food and Drug Administration, Guidance for Industry:
`Container Closure Systems for Packaging Human and Biologics –
`Chemistry, Manufacturing, and Controls Documentation (May 1999),
`available at
`https://www.fda.gov/downloads/drugs/guidances/ucm070551.pdf
`Ex. 1042 International Standard ISO-7864, Sterile hypodermic needles for
`single use, ISO 7864:1993(E) (“ISO-7864”)
`Ex. 1043 International Standard ISO-9626, Stainless steel needle tubing for the
`manufacture of medical devices – Amendment 1, ISO
`9626:1991/Amd.1:2001(E) (“ISO-9626”)
`Ex. 1044 Advait Badkar, et al. Development of Biotechnology Products in Pre-
`filled Syringes: Technical Considerations and Approaches,
`American Association of Pharmaceutical Sciences, June 2011, 12(2):
`564-572 (“Badkar”)_
`Ex. 1045 William Leventon, “Medical Device Sterilization: What
`Manufacturers Need to Know” (MDDI online, Sept. 1, 2002),
`available at https://www.mddionline.com/medical-device-
`sterilization-what-manufacturers-need-know (“Leventon”)
`Ex. 1046 Pamela Carter, et al. The lowdown on low temperature sterilization
`for packaged devices, Healthcare Purchasing News, July 2008, 42-45.
`(“Carter”)
`Ex. 1047 U.S. Patent Publication No. 2005/0182370 to Hato (“Hato”)
`
`Ex. 1048 U.S. Department of Labor, Occupational Safety & Health
`Administration, Ethylene Oxide (EtO): Understanding OSHA’s
`Exposure monitoring Requirements, 2007 OSHA3325-01N (2007),
`available at https://www.osha.gov/Publications/ethylene_oxide.html
`(“OSHA Guidelines”)
`Ex. 1049 Bryon Lambert, et al. Radiation and Ethylene Oxide Terminal
`Sterilization Experiences with Drug Eluting Stent Products,
`American Association of Pharmaceutical Sciences, December 2011,
`12(4):1116-1126 (“Lambert”)_
`Ex. 1050 K. Kereluk, et al. Microbiological Aspects of Ethylene Oxide
`Sterilization: I. Experimental Apparatus & Methods, Applied
`Microbiology 1970, 19(1):146-151. (“Kereluk”)
`
`
`
`
`v
`
`

`

`
`
`Description
`Exhibit
`Ex. 1051 Carl Hultman, et al. The Physical Chemistry of Decontamination with
`Gaseous Hydrogen Peroxide, Pharmaceutical Engineering,
`January/February 2007, 27(1):1-6 (“Hultman”)
`Ex. 1052 John R. Gillis & Gregg Mosley, Validation of Pharmaceutical
`Processes, Chapter 16 – Validation of Ethylene Oxide Sterilization
`Processes (2011), pp.241-262.
`Ex. 1053 FDA Pesticide Analytical Manual Vol. 1, Chapter 6 - HPLC,
`available at
`https://www.fda.gov/downloads/Food/FoodScienceResearch/
`ucm113651.pdf
`Ex. 1054 Kim, Leo & D’Amore, Patricia, ASIP Centennial Commentary – A
`Brief History of Anti-VEGF for the Treatment of Ocular
`Angiogenesis, The American Journal of Pathology, August 2012
`182(2):376-379, available at (note: published online July 2, 2012
`https://ajp.amjpathol.org/article/S0002-9440(12)00442-7/fulltext )
`Ex. 1055 J.S. Penn, et al. Vascular Endothelial Growth Factor in Eye Disease,
`Prog. Retin Eye Res., July 2008, 27(4):331-371. (“Penn2008”)
`Ex. 1056 U.S. Food and Drug Administration, Trivaris ® Highlights of the
`Prescribing Information, (May 2008) (“Trivaris label”)
`Ex. 1057 Internet Archive WayBack Machine, May 17, 2011 Record of U.S.
`Pharmacopeia, Understanding USP–NF, available at
`https://web.archive.org/web/20110517215303/http://www.usp.org/
`USPNF/understandingUSPNF.html
`Ex. 1058 Christine I. Falkner-Radler, et al. Needle Size in Intravitreal
`Injections-Preliminary Results of a Randomized Clinical Trial,
`AVRO Annual Meeting Abstract, March 2012, 54(884), available at
`https://iovs.arvojournals.org/article.aspx?articleid=2350271 (“ARVO
`abstract”)
`Ex. 1059 Carsten H. Meyer et al., Steps for a Safe Intravitreal Injection
`Technique – A look at how European and American approaches
`compare, Retinal Physician (July 1, 2009), available at
`https://www.retinalphysician.com/issues/2009/july-aug/steps-for-a-
`safe-intravitreal-injection-technique (“Meyer”)
`Ex. 1060 Curriculum Vitae of James L. Mullins, Ph.D.
`
`Ex. 1061 DUPONT™ TYVEK® COMPLIANCE TO ISO 11607-1:2006
`(2011)
`
`
`
`
`vi
`
`

`

`
`
`Description
`Exhibit
`Ex. 1062 Center for Drug Evaluation and Research, Application Number: 21-
`756, Approved Labeling, Macugen® (pegaptanib sodium injection)
`(December 17, 2004)
`Ex. 1063 Evangelos S. Gragoudas et al., Pegaptanib for Neovascular Age-
`Related Macular Degeneration, New England Journal of Medicine
`2004; 351:2805-16, with Supplementary Appendix.
`Ex. 1064 Bruno Reuter and Claudia Petersen. “Die Silikonisierung von
`Spritzen: Trends, Methoden, Analyseverfahren,” TechnoPharm 2, Nr.
`4 (2012): 238-244. (Untranslated German version.)
`Ex. 1065 Hearing by Teleconference, IPR2020-01317 and IPR2020-01318,
`October 29, 2020
`Ex. 1066 November 24, 2020 Email re Motion to Terminate Proceedings in
`IPR2020-01318
`Ex. 1067 Letter to E. Holland re Pending IPR Petitions, November 20, 2020
`
`Ex. 1068 U.S. Application 13/382,380 Prosecution History
`
`Ex. 1069 Novartis’s Opening Markman Brief, November 10, 2020
`
`Ex. 1070 Sigg Declaration From 13/382,380 Prosecution History
`
`Ex. 1071 Joint Disclosure of Proposed Claim Construction Chart
`
`
`
`
`
`
`vii
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`Regeneron Pharmaceuticals, Inc. (“Regeneron”) discovered and developed
`
`the VEGF-antagonist known as EYLEA® (aflibercept)—the leading treatment for
`
`a variety of severe eye diseases that can cause vision loss and blindness—which it
`
`sells in pre-filled syringes. When Novartis on June 19, 2020 filed ITC and district
`
`court complaints alleging infringement of U.S. Patent No. 9,220,631 (“the 631
`
`patent”), Regeneron prepared and filed its two IPR petitions, IPR2020-01317 and
`
`IPR2020-01318, only 27 days later and before institution of the ITC proceeding.
`
`With respect to the merits of Novartis’s §§ 314(a) and 325(d) arguments,
`
`Regeneron has strived to streamline the proceedings. On July 30, 2020, the NDNY
`
`district court litigation was stayed (with Novartis’s agreement) on Regeneron’s
`
`motion. Regeneron also asked for and received the Board’s permission to file a
`
`motion to terminate IPR2020-01318. Ex. 1066. Regeneron has stipulated that if the
`
`Board institutes trial, it will not pursue at the ITC the invalidity grounds set forth in
`
`both petitions. Ex. 1067. These efforts will focus the Board’s and parties’ resources
`
`on IPR2020-01317, and eliminate duplicative efforts across the proceedings.
`
`
`
`Moreover, as explained herein, Novartis successfully hid material and non-
`
`cumulative prior art, including Sigg (Ex. 1007), from the Examiner during
`
`prosecution of the 631 application. It now seeks to repeat that success by relying
`
`on 35 U.S.C. §§ 314(a) and 325(d) to avoid the Board considering the full scope of
`
`1
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`prior art against the 631 patent claims. Novartis’s request for discretionary denial
`
`pursuant to 35 U.S.C. §§ 314(a), 325(d), should be rejected, and trial instituted.
`
`ARGUMENT
`Novartis correctly identifies the Board’s precedential decisions in Becton,
`
`
`
`Dickinson and Co. v. B. Braun Melsungen AG, IPR2017-01586, Paper 8 (P.T.A.B.
`
`Dec. 15, 2017) and Apple Inc. v. Fintiv, Inc., IPR2020-00019, Paper 11 (P.T.A.B.
`
`May 13, 2020) as setting out the factors the Board considers under §§ 325(d)
`
`and 314(a), respectively. See POPR at 7-8, 16. But Novartis is wrong in asserting
`
`that the factors favor denial of institution. Instead, the opposite is true.
`
`The Becton Dickinson Factors Favor Institution
`A.
`As set forth below, Novartis’s § 325(d) argument is laden with
`
`
`
`mischaracterizations and omits highly relevant facts regarding the prosecution of
`
`the 631 application and another Novartis application sharing a common inventor.
`
`
`
`
`
`
`
`1.
`
`Becton Dickinson Factors (a) – (c)
`
`Novartis does not dispute that the primary references in the Petition (Sigg
`
`and Boulange, Exs. 1007 and 1008) were not considered by the Examiner. This
`
`alone supports the Board not exercising its discretion to deny institution. Oticon
`
`Medical AB v. Cochlear Ltd., IPR2019-00975, Paper 15 at 19-20 (P.T.A.B. Oct.
`
`19, 2019) (precedential). And Novartis’s attempt to equate that art to what was
`
`before the Examiner wholly fails.
`
`
`
`
`2
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`
`
`Novartis argues that the references in the IPR are not “materially different”
`
`from what was before the Examiner and that the “Examiner had already been
`
`aware of the terminal sterilization art.” POPR at 17, 19. This is utterly false. There
`
`was not a single prior art reference before the Examiner disclosing terminal
`
`sterilization, much less terminal sterilization of a pre-filled syringe. Tellingly,
`
`Novartis does not identify a single prior art reference in its POPR disclosing
`
`terminal sterilization. Novartis failed to identify such art even though terminal
`
`sterilization was critical to the Examiner’s allowance of the claims. See Ex.
`
`1002.1358 (finally rejecting all claims because “the features upon which applicant
`
`relies (i.e., the prefilled syringe is terminally sterilized) are not recited in the
`
`rejected claim(s)”); Ex. 1002.1370 (amending claim 1 to include a “prefilled,
`
`terminally sterilized syringe”); Ex. 1002.1461-62 (IDS filed with amendment with
`
`no terminal sterilization art included); Ex. 1002.1458 (allowing claims).
`
`
`
`What’s more, there can be no question that Novartis and the first-named
`
`inventor (Juergen Sigg) were well aware of terminal sterilization prior art. Novartis
`
`had a co-pending application (U.S. Pat. App. 13/382,380 (the “380 application”))1
`
`that overlapped with the 631 application prosecution. The 380 application contains
`
`
`1 The 380 application claims priority to the same EPO application that published as
`
`Sigg (Ex. 1007). Compare Ex. 1068.001 to Ex. 1007.001.
`
`
`
`
`3
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`the same disclosure as Sigg, and names Dr. Sigg as the sole inventor. See Ex.
`
`1068.169. Across five office actions involving a different examiner, the 380
`
`application claims (directed to terminally sterilizing a pre-filled syringe containing
`
`a VEGF-antagonist) were rejected as obvious in view of Metzner (Ex. 1018). Ex.
`
`1068.346-348, 376-380, 411-415, 505-510, 534-539, 559-564. Novartis did not
`
`respond to the fifth office action dated April 2, 2014, and the application was
`
`abandoned on November 6, 2014. Ex. 1068.573. Novartis and Dr. Sigg then
`
`pivoted to the 631 application, amending the claims on July 16, 2015 to add
`
`terminal sterilization, without disclosing Sigg, Metzner, the 380 application and
`
`prosecution, or the prior art of record therein. The Board now has an opportunity to
`
`consider that art for the first time in this IPR.
`
`
`
`Novartis also argues that the 631 patent itself shows Regeneron’s terminal
`
`sterilization art is cumulative of the art before the Examiner. That argument –
`
`based solely on the statement at col. 9:49-52 of 631 patent – is equally baseless.
`
`POPR at 18. There is a reason Novartis failed to quote that passage in the POPR,
`
`because the plain language refutes Novartis’s argument. Rather than containing an
`
`acknowledgement that terminal sterilization of a prefilled syringe containing a
`
`VEGF-antagonist was known in the art, the passage merely states that “a terminal
`
`sterilisation process may be used to sterilise the syringe and such a process may
`
`use a known process such as an ethylene oxide (EtO) or a hydrogen peroxide
`
`
`
`
`4
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`(H2O2) sterilisation process.” Ex. 1001 at 9:49-52. This only confirms that EtO and
`
`H2O2 processes were generally known; it does not state that they were known to be
`
`used on a prefilled syringe or a prefilled syringe containing a VEGF-antagonist.
`
`Worse, whereas Novartis represents to the Board that col. 9:49-52 is an
`
`acknowledgement of the known use of terminal sterilization on a pre-filled syringe,
`
`Novartis has told the ITC that the passage means the opposite. Specifically,
`
`Novartis cited col. 9:49-52 for “the novel disclosure of a terminally-sterilized pre-
`
`filled syringe.” Ex. 1069.011 (emphasis added). The Board should not excuse
`
`Novartis from taking such contrary positions before two different agencies.
`
`
`
`Next, Novartis argues that Sigg “provides nothing beyond” that terminal
`
`sterilization was generally known, and that Sigg discloses “nothing …other than
`
`the aspiration to terminally sterilize a VEGF antagonist-filled syringe….” POPR at
`
`18. That too is false. Sigg discloses a detailed process with test results for
`
`terminally sterilizing a PFS containing a VEGF-antagonist. Ex. 1007 at 9:11-14,
`
`12:15-16:21, 20:10-21:11. In contrast, the 631 patent contains no detailed process
`
`for terminal sterilization of a PFS containing a VEGF-antagonist, nor does it (as
`
`explained above) disclose that such a process was known in the art. Further,
`
`Novartis’s “aspirational” argument is directly contradicted by Dr. Sigg himself
`
`during prosecution of the 380 application. There, Dr. Sigg declared that the
`
`“present application disclosed for the first time, and contrary to conventional
`
`
`
`
`5
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`thinking, that it is possible to obtain sufficient sterilization of the outer surface of
`
`a syringe in secondary packaging….” Ex. 1070.004 (emphasis added).
`
`
`
`Turning to Novartis’s arguments concerning the siliconization prior art in
`
`the petition, Novartis attempts to equate the teachings of Boulange (Ex. 1008) with
`
`Hioki (Ex. 1020), which the Examiner relied on for rejecting the pending claims.
`
`POPR at 19-21. But Novartis omits that Boulange discloses in a single reference
`
`all of the claimed syringe features: a glass body; a maximum fill volume of about 1
`
`mL; less than about 100 µg of silicone oil; and break loose and slide forces less
`
`than 11N and 5N. Petition at 32-36. Hioki disclosed a plastic (resin) barrel (Ex.
`
`1020, Abstract) and did not contain any specific disclosure of slide forces; only
`
`that “it is possible to ensure sufficient slidability with the gasket.” Ex. 1020,
`
`[0022]; see id., [0061] (“the sliding resistance between gasket 24 and barrel 20 can
`
`be reduced.”). Further, Boulange provides teachings that the glass syringe would
`
`be successfully terminally sterilized. Petition at 41. In contrast, Novartis told the
`
`Examiner that terminal sterilization of a plastic syringe (like that in Hioki) “is
`
`difficult” because the “seal is known to leak” which can “denature the protein.” Ex.
`
`1002.1275. Hioki plainly does not contain “exactly the same teaching for which
`
`[Regeneron] relies on Boulange,” as Novartis argues. POPR at 20-21.
`
`
`
`Finally, Novartis’s reliance on Badkar (Ex. 1044) is also misplaced. POPR
`
`at 21, 26. Contrary to Novartis’s arguments, the 631 patent does not contain an
`
`
`
`
`6
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`admission that Badkar discloses a baked-on siliconization method that reduced
`
`silicone oil without adversely impacting slide forces. POPR at 26. Instead, the
`
`portion of the specification Novartis cites—col. 4:56-60—represents that Badkar at
`
`most only discloses that the industry used 100-800 µg or “typically” 500-1000 µg
`
`of silicone oil. Ex. 1001 at 4:46-60. Of course, claim 1 requires from “about 1 to
`
`100 µg silicone oil.” Thus, rather than describe the full disclosure of Badkar,
`
`including its discussion of a baked-on method and using “ten-fold less free silicone
`
`oil, [with] no deleterious impact on product quality,” Ex. 1044.008, the 631
`
`inventors attempted to obscure these teachings in Badkar. Indeed, the specification
`
`wrongly represents that it was the applicants that discovered it was possible to
`
`reduce silicone oil without impacting forces. Ex. 1001 at 5:15-50.
`
`
`
`
`
`
`
`2.
`
`Becton Dickinson Factors (d) – (e)
`
`Novartis’s mischaracterizations continue in its prosecution history analysis.
`
`Novartis represents that “terminal sterilization of prefilled syringes continued to be
`
`a focal point of both the Patent Owner’s and the Examiner’s arguments during
`
`prosecution.” POPR at 18. Not so. The Examiner’s first three office actions (see
`
`Ex. 1002.1245-1253; 1280-1288; 1305-1311) were entirely focused on silicon-
`
`ization of the syringe barrel. Terminal sterilization was not discussed at all by the
`
`Examiner, which is not surprising since it was not claimed. Indeed, in the fourth
`
`office action, the Examiner questioned why Novartis’s prior arguments focused on
`
`
`
`
`7
`
`

`

`IPR2020-01317
`U.S. Patent No. 9,220,631
`
`terminal sterilization because “it is noted that the features upon which applicant
`
`relies (i.e., the prefilled syringe is terminally sterilized) are not recited in the
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`rejected claim(s).” Ex. 1002.1358. It was only then that Novartis added terminal
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`sterilization to the claims and they were allowed. As Novartis failed to disclose any
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`terminal sterilization prior art, it was hardly a focal point of examination.
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`Next, Novartis cites its August 13, 2014 argument to the Examiner as
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`allegedly showing that “terminal sterilization of glass syringes containing sensitive
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`biologics, like VEGF antagonists, was known.” POPR at 18. Instead, the statement
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`warns that terminal sterilization of plastic syringes can denature the VEGF-
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`antagonist. Ex. 1002.1275. It was thus known that “syringes which are prefilled
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`with biologics are comprised of glass barrels.” Id. This passage plainly does not
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`disclose that terminal sterilization of prefilled glass syringes was known.
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`3.
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`Becton Dickinson Factor (f) and Conclusion re § 325(d)
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`The facts show that Novartis and Dr. Sigg succeeded in hiding terminal
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`sterilization art during the 631 prosecution. This is especially concerning given
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`their knowledge of terminal sterilization art (including Sigg, Ex. 1007) and the
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`prosecution of the 380 application. Novartis is trying once again to hide terminal
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`sterilization art, by relying on §§ 314, 325 in an attempt to avoid having the Board
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`substantively consider the claims with a full record of prior art. Because the Becton
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`Dickinson factors plainly do not support discretionary denial, the Board should
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`reject Novartis’s § 325(d) arguments and institute trial, so that the Board may fully
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`consider the prior art teaching terminal sterilization of prefilled syringes, low
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`levels of silicone oil, and low break loose and slide forces.
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`B.
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`The Fintiv Factors Favor Institution
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`1.
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`Factor 1: Whether a Stay Was Granted
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`The two other proceedings concerning the 631 patent are the ITC
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`investigation and the stayed district court case. The fact that the ITC investigation
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`was not stayed is neither surprising nor compelling. Asking for a stay of the ITC
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`investigation would have been futile. The ITC normally does not stay
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`investigations when IPR proceedings are pending because 19 U.S.C. § 1337(b)(1)
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`requires that ITC investigations be completed expeditiously. See, e.g., Certain
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`Memory Modules and Components Thereof, Inv. No. 337-TA-1089, Order No. 49
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`(Apr. 11, 2019) (denying motion for stay). Nonetheless, when a patent is the
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`subject of both IPR and ITC proceedings, the ITC recognizes the paramount role of
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`the Board “as the lead agency in assessing the patentability, or validity, of
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`proposed or issued claims.” Certain Unmanned Aerial Vehicles and Components
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`Thereof, Inv. No. 337-TA-1133, Comm’n Op. at 37 (Sept. 8, 2020) (emphasis
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`added). The ITC thus fully appreciates that its proceedings may be directly
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`impacted by parallel Board proceedings, just as Congress intended. See id. at 38
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`(quoting S. REP. No. 110-259, at 20 (2008)).
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`The ITC’s deferral to the Board’s expertise makes perfect sense. First, it is
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`consistent with Congressional intent. See 157 Cong. Rec. S1352 (daily ed. Mar. 8,
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`2011) (statement of Sen. Udall) (“Inter partes … proceedings are intended to serve
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`as a less-expensive alternative to courtroom litigation and provide additional
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`access to the expertise of the Patent Office on questions of patentability.”). Second,
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`the ITC’s validity determinations have no preclusive effect. Fintiv at 8-9. For this
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`reason, the ITC suspended its remedial orders in Unmanned Aerial Vehicles
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`following a FWD invalidating all asserted claims of the patent at issue, noting that
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`it may issue remedies only if it finds the accused products “infringe a valid and
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`enforceable” patent. Comm’ Op. at 35 (emphasis in original); id. at 38 (suspending
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`the remedial orders “gives effect to the Congressional goal” of using IPRs as a
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`substitute for invalidity litigation).
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`
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`Previous Board decisions have perhaps discounted the non-preclusive effect
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`of ITC invalidity findings because “as a practical matter, it is difficult to maintain a
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`district court proceeding on patent claims determined to be invalid at the ITC.”
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`Fintiv at 9. But there are numerous cases where the patentee has forged ahead with
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`district court actions following an ITC finding of invalidity – even when upheld by
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`the Federal Circuit. See In re Convertible Rowing Exerciser Patent Litig., 721 F.
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`Supp. 596, 602 (D. Del. 1989) (holding that the Federal Circuit’s affirmance of an
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`ITC invalidity holding “does not entitle the ITC determination to preclusive
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`10
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`effect.”); Code Alarm, Inc. v. Directed Elecs., Inc., 919 F. Supp. 259 (E.D. Mich.
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`1996); Hyosung TNS, Inc. v. Diebold Nixdorf, Inc., Case No. 3:16-CV-0364-N,
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`Memo. Op. and Order (N.D. Tex. Dec. 5, 2019) (denying motion for summary
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`judgment after patent found invalid by ITC and affirmed by Federal Circuit
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`because “there may be evidence not presented on the ITC record considered by the
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`Federal Circuit that could merit a … different conclusion regarding … validity”).
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`
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`Thus, even if the ITC invalidates the 631 patent, Novartis can still pursue its
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`district court case. But if the Board exercises its discretion to deny institution,
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`Regeneron would lose its Congressionally-endorsed ability to challenge the patent
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`in an IPR simply because Novartis chose to also file an ITC action, even when
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`Regeneron filed its IPR petition a mere 27 days after the ITC complaint was filed.
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`Such a result is against both Congressional intent and the ITC’s endorsement of the
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`PTAB’s lead role in handling validity questions, and would amount to a de facto
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`rule that patents could be shielded from IPR scrutiny by filing an ITC action.
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`
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`Factor 3: Investment in the Parallel Proceeding
`2.
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`An ITC respondent could realistically not have brought its IPR challenges
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`faster than Regeneron. When it filed its petition, the ITC had not even instituted an
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`investigation; as such, there was no schedule in place. Fintiv at 11 (“If the evidence
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`shows that the petitioner filed the petition expeditiously, … this fact has weighed
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`against exercising the authority to deny institution.”).
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`ITC proceedings are statutorily required to be completed expeditiously, 19
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`U.S.C. § 1337(b)(1), and it is thus inevitable that the parties will have invested
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`resources in the ongoing ITC investigation. But it should be self-evident that
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`Regeneron also invested enormous time and resources in preparing and filing the
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`two IPR petitions less than a month after learning of the complaints. As explained
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`above, Congress and the ITC both agree that the Board should be the “lead
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`agency” analyzing Regeneron’s obviousness arguments. The ALJ and ITC so far
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`have invested no time or resources analyzing obviousness issues. And with respect
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`to the grounds in the petitions, Regeneron stipulated that it will not pursue those
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`grounds in the ITC if the Board institutes trial. Ex. 1067. As such, there is no risk
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`that instituting trial here will “lead to duplicative costs.” Fintiv at 10.
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`
`
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`Factor 4: There Will Be No Overlap Between Issues
`3.
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`Regeneron has stipulated that, if the Board grants the motion to terminate
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`IPR2020-01318 and institutes trial here, it will not pursue in the ITC the invalidity
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`grounds set forth in either petition; the Board and the ITC thus will not address the
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`same invalidity arguments. There is also no risk of inconsistent claim construction
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`positions between the Board and the ITC, as there is no overlap between the terms
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`identified in the Parties’ ITC Markman briefing and the terms identified in the
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`petition. Compare Ex. 1071 with Petition at 27-28. Thus, there are no “concerns of
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`inefficiency and the possibility of conflicting decisions” between the Board and
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`12
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`ITC. Fintiv at 12; Sand Revolution II, LLC v. Continental Intermodal Group –
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`Trucking LLC, IPR2019-01393, Paper 24 at 12 (P.T.A.B. June 16, 2020).
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`
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`Further, Regeneron’s petition challenges every claim of the 631 patent.
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`Hence, if trial is instituted and the Board invalidates all the claims, there is no risk
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`that Novartis could assert in the district court case the claims it did not assert in the
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`ITC. Accordingly, this factor weighs in favor of institution.
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`4.
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`
`Factor 2: The ITC and Board Schedules Are as Close in
`Proximity as Practicably Possible
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`The Board and ITC schedules are as close in proximity as practicably
`
`possible because Regeneron filed its petition less than a month after Novartis filed
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`its ITC complaint and before institution of the ITC proceedings. The ALJ’s
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`schedule indicates that, when the Board issues its ID by January 22, 2021, the ITC
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`Investigation will be in the middle of expert discovery. If the Board institutes trial,
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`the FWD will be due January 22, 2022—less than two months after the November
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`29, 2021 target date in the ITC investigation, and before expiration of the 60-day
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`Presidential review period (which will expire approximately January 29, 2022) if
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`the ITC enters an exclusion order. 19 U.S.C. § 1337(j). Notably, Novartis
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`misrepresents the ITC schedule when it states that a FWD “would be due . . .
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`approximately six months after the ITC issues its decision.” POPR at 10 (emphasis
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`added). Instead, the FWD is due only two months after the Commission’s (i.e., the
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`ITC’s) final determination.
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`Regeneron’s expediency in filing its petition distinguishes the facts here
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`from the cases that Novartis cites in its POPR. See Apple Inc. v.