`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`SAMSUNG BIOEPIS CO., LTD., CELLTRION INC,
`and BIOCON BIOLOGICS INC.
`Petitioner,
`
`v.
`REGENERON PHARMACEUTICALS, INC.
`Patent Owner.
`
`
`U.S. Patent No. 11,253,572
`
`_______________
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`Inter Partes Review No. IPR2023-008841
`____________________________________________________________
`PATENT OWNER’S RESPONSE
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`1 IPR2024-00260 and IPR2024-00298 have been joined with IPR2023-00884.
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`IPR2023-00884
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`TABLE OF CONTENTS
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`
`I.
`II.
`
`Introduction ...................................................................................................... 1
`Background ...................................................................................................... 3
`A.
`EYLEA® ............................................................................................... 3
`1.
`Development of Eylea® for AMD ............................................. 3
`2.
`Development of Eylea® for DME .............................................. 8
`3.
`Eylea®’s Commercial Success ................................................. 12
`’572 Patent ........................................................................................... 12
`B.
`III. Priority Date ................................................................................................... 13
`IV. Level of Ordinary Skill in the Art ................................................................. 14
`V.
`Claim Construction ........................................................................................ 15
`A.
`The Results Limitations Have Patentable Weight (all claims) ............ 15
`B.
`“A method of treating” (all claims) ..................................................... 17
`C.
`“approximately 4 weeks following the immediately preceding
`dose . . . approximately 8 weeks following the immediately
`preceding dose” (claims 1, 15 26, 29) ................................................. 18
`VI. Petitioner Has Not Proven the Challenged Claims Unpatentable ................. 20
`A. Ground II: The December 2010 PR Is Not Prior Art .......................... 20
`1.
`Dr. Yancopoulos Reduced to Practice the Claimed
`Inventions Before December 20, 2010 ..................................... 21
`The December 2010 PR Discloses Dr.
`Yancopoulos’s Work ................................................................ 27
`B. Ground III: The November 2010 PR Is Not Prior Art ........................ 31
`1.
`Dr. Yancopoulos Reduced to Practice Claims 1-3,
`5-8, 10-14, and 26-30 Before November 22, 2010 ................... 31
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`2.
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`2.
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`The November 2010 PR Discloses Dr.
`Yancopoulos’s Own Work ........................................................ 37
`C. Ground IV ............................................................................................ 38
`1.
`The Claimed Results Were Not Obvious .................................. 39
`2.
`Ground IV Is a Disguised Inherency Argument
`That Fails ................................................................................... 47
`D. Ground V ............................................................................................. 53
`1.
`Samsung Has Not Shown Obviousness Over the
`2009 PR, Dixon, and 2007 ARVO ........................................... 54
`2010 ARVO Is Not Prior Art .................................................... 55
`2.
`Ground VI ............................................................................................ 58
`1.
`Samsung’s Ground VI Arguments Fail for the
`Same Reasons as for Grounds II and IV ................................... 59
`Neither Dixon Nor Hecht Shows the Claimed
`Formulations Were Obvious ..................................................... 59
`Ground VII .......................................................................................... 63
`F.
`G. Ground VIII ......................................................................................... 64
`1.
`Dixon Does Not Disclose the Claimed Results ........................ 64
`2.
`The December 2010 PR Is Not Prior Art .................................. 64
`H. Ground IX: The 2009 PR, Shams, and Elman 2010 Do Not
`Disclose Four Secondary Doses .......................................................... 64
`1.
`2009 PR ..................................................................................... 65
`2.
`Shams ........................................................................................ 66
`3.
`Elman ........................................................................................ 67
`4.
`The Mylan Order ....................................................................... 69
`Grounds X & XI: The Results Limitations Have Patentable
`Weight ................................................................................................. 70
`VII. Eylea®’s Commercial Success Objectively Demonstrates Non-
`Obviousness ................................................................................................... 70
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`E.
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`2.
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`I.
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`Eylea® has as nexus to the challenged claims .................................... 70
`A.
`Eylea® is a commercial success ......................................................... 71
`B.
`VIII. Conclusion ..................................................................................................... 73
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`TABLE OF AUTHORITIES
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`
`
` Page(s)
`
`Cases
`Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co.,
`598 F.3d 1336 (Fed. Cir. 2010) .......................................................................... 13
`Bristol-Myers Squibb Co. v. Boehringer Ingelheim Corp.,
`86 F. Supp. 2d 433 (D.N.J. 2000) ....................................................................... 16
`Bristol-Myers Squibb Co. v. Ben Venue Labs. Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) .......................................................................... 16
`Barry v. Medtronic, Inc.,
`914 F.3d 1310 (Fed. Cir. 2019) .......................................................................... 25
`Chemours Co. FC, LLC v. Daikin Indus., Ltd.,
`4 F.4th 1370 (Fed. Cir. 2021) ............................................................................. 71
`Comark Comm’ns, Inc. v. Harris Corp.,
`156 F.3d 1182 (Fed. Cir. 1998) .......................................................................... 16
`Cont’l Can Co. USA v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir. 1991) .......................................................................... 70
`Duncan Parking Techs., Inc. v. IPS Grp., Inc.,
`914 F.3d 1347 (Fed. Cir. 2019) .......................................................................... 56
`E.I. du Pont de Nemours & Co. v. Unifrax I LLC,
`921 F.3d 1060 (Fed. Cir. 2019) .......................................................................... 21
`Foundation Medicine, Inc. v. Guardant Health, Inc.,
`IPR2019-00636, Paper 10 (P.T.A.B. Aug. 20, 2019) ................................... 49-50
`Foundation Medicine, Inc. v. Guardant Health, Inc.,
`IPR2019-00636, Paper 14 (P.T.A.B. Dec. 20, 2019) ......................................... 50
`Gilead Sciences, Inc. v. United States,
`2020 WL 582217 (P.T.A.B. Feb. 5, 2020) ......................................................... 51
`Hewlett-Packard Co. v. Mustek, Systems, Inc,
`340 F.3d 1314 (Fed. Cir. 2017) .................................................................... 47-48
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`Honeywell Int’l Inc. v. Mexichem Amanco Holding S.A.,
`865 F.3d 1348 (Fed. Cir. 2017) .................................................................... 50, 52
`In re Copaxone Consol. Cases,
`906 F.3d 1013 (Fed. Cir. 2018) .......................................................................... 16
`In re DeBaun,
`687 F.2d 459 (C.C.P.A. 1982) ................................................................ 22, 38, 57
`In re Katz,
`687 F.2d 450 (C.C.P.A. 1982) ...................................................................... 27, 55
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 16
`In re Magnum Oil,
`829 F.3d (Fed. Cir. 2016) ............................................................................passim
`LA Biomed v. Eli Lilly,
`849 F.3d 1049 (Fed. Cir. 2017) .......................................................................... 15
`Lockheed Martin Corp. v. Space Sys./Loral, Inc.,
`324 F.3d 1308 (Fed. Cir. 2003) .......................................................................... 16
`Medtronic, Inc. v. Teleflex Innovations S.À.R.L,
`68 F.4th 1298 (Fed. Cir. 2023) ........................................................................... 21
`MEHL/Biophile Int’l Corp. v. Milgraum,
`192 F.3d 1362 (Fed. Cir. 1999) .......................................................................... 50
`Millenium Pharm., Inc. v. Sandoz Inc.,
`862 F.3d 1356 (Fed. Cir. 2017) .......................................................................... 52
`Mylan Pharm. Inc. v. Regeneron Pharm., Inc.,
`IPR2022-01226, Paper 101 (P.T.A.B. Jan. 9, 2024) .................................... 51-53
`Novartis Pharms. Corp. v. West-Ward Pharms. Int’l Ltd.,
`287 F. Supp. 3d 505 (D. Del. 2017) .................................................................... 41
`Novartis Pharms. Corp. v. West-Ward Pharms. Int’l Ltd.,
`923 F.3d 1051 (Fed. Cir. 2019) .......................................................................... 41
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`PAR Pharm., Inc. v. TWI Pharms., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) ...................................................................passim
`ParkerVision, Inc. v. Qualcomm Inc.,
`903 F.3d 1354 (Fed. Cir. 2018) .......................................................................... 48
`Regeneron Pharm., Inc. v. Mylan Pharm. Inc. et al,
`No. 22-cv-00061, Dkt. No. 427, (N.D.V.A. Apr. 19, 2023) .............................. 17
`Regeneron Pharm., Inc. v. Mylan Pharm. Inc. et al,
`No. 22-cv-00061, Dkt. No. 692 (N.D.V.A. Jan. 31, 2024) ............... 62-63, 70-71
`Roxane Lab’ys, Inc. v. Vanda Pharms. Inc.,
`IPR2016-00690 (Paper 8), 2016 WL 5226531 (P.T.A.B. Aug. 30,
`2016) ................................................................................................................... 67
`Sanofi v. Watson Labs., Inc.,
`875 F.3d 636 (Fed. Cir. 2017) ...................................................................... 42, 54
`Snitzer v. Etzel,
`465 F.2d 899 (CCPA 1972) ................................................................................ 13
`Syntex (U.S.A.) LLC v. Apotex, Inc.,
`407 F.3d 1371 (Fed. Cir. 2005) .......................................................................... 16
`Unwired Planet, LLC v. Google Inc.,
`841 F.3d 995 (Fed. Cir. 2016) ...................................................................... 47-49
`Volvo Penta of the Ams., LLC v. Brunswick Corp.,
`81 F.4th 1202 (Fed. Cir. 2023) ........................................................................... 70
`Xerox Corp. v. Bytemark, Inc.,
`IPR2022-00624, Paper 9 (Aug. 23, 2022) .......................................................... 47
`Other Authorities
`35 U.S.C. § 102 .................................................................................................passim
`35 U.S.C. § 103 .................................................................................................passim
`35 U.S.C. § 312 .................................................................................................. 45, 63
`37 C.F.R. § 1.131(b) ................................................................................................ 21
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`84 FR 64280, 73 ................................................................................................passim
`MPEP § 717.01(a)(1) ................................................................................... 31, 38, 58
`MPEP § 2159 ........................................................................................................... 14
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`TABLE OF ABBREVIATIONS
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`Petition (Paper 2)
`Decision Granting Institution (Paper 13)
`2009 Press Release (Exhibit 1005)
`December 2010 Press Release (Exhibit 1006)
`November 2010 Press Release (Exhibit 1007)
`2010 ARVO Abstract (Exhibit 1010)
`2006 Press Release (Exhibit 1027)
`2007 ARVO Abstract (Exhibit 1030)
`Person of ordinary skill in the art
`Wet age-related macular degeneration
`Diabetic macular edema
`
`“Pet.”
`“DI”
`“2009 PR”
`“December 2010 PR”
`“November 2010 PR”
`“2010 ARVO”
`“2006 PR”
`“2007 ARVO”
`“POSA”
`“wAMD”
`“DME”
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`I.
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`INTRODUCTION
`The challenged patent relates to Regeneron’s inventive methods for treating
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`angiogenic eye disorders and preventing blindness. The claimed methods involve
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`injecting patients suffering from angiogenic eye disorders with fixed numbers of
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`monthly “loading doses” of aflibercept (also at times called “VEGF Trap-Eye” or
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`“Eylea®”) and then extending the dosing interval to every-two-month
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`“maintenance doses.” This regimen halves the number of ongoing injections
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`needed to treat wAMD and DME.
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`In early 2011, Regeneron filed a provisional patent application disclosing the
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`new regimen and related clinical trial results. That application matured into the
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`’572 patent, which claims both that regimen and achieving certain visual acuity
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`outcomes (the “result limitations”). Samsung now seeks to cancel all of those
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`claims and has taken a kitchen-sink approach to doing so, spreading its challenge
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`across more than 12 references and 11 grounds, and across more than 32
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`anticipation and obviousness theories. Despite the Board’s invitation for Samsung
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`to drop unnecessary or irrelevant grounds (see DI at 15), Samsung has not done so.
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`The Board should reject Samsung’s challenge for at least four reasons:
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`First, many of Samsung’s references are not prior art, which is fatal to some
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`or all of Samsung’s arguments for Grounds II-III and V-VIII. ARVO 2010, the
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`November 2010 PR, and the December 2010 PR published less than a year before
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`the ’572 patent’s priority date, and they report results of Regeneron’s own clinical
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`trials. Regeneron and Dr. Yancopoulos perfected the claimed inventions before the
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`results were reported. Thus, each invention was reduced to practice before the
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`references were published, and the relied-upon disclosures were derived from the
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`inventor. In its DI, the Panel noted the need for evidence so proving; Regeneron
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`provides that evidence here.
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`Second, with respect to Grounds IV-VIII, Samsung has not shown that the
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`results limitations are obvious over partial results from different trials. The partial
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`data in Samsung’s references derive from different dosing regimens than claimed,
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`and they in no way give the POSA a reasonable expectation of success of
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`achieving the results limitations, much less show the claimed regimens always
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`yield those results. Samsung’s arguments to the contrary are conclusory and
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`unpersuasive, particularly for the challenged claims with results limitations at 52
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`weeks, which Samsung barely addresses.
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`Third, Ground IX fails because Samsung has not shown that it would have
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`been obvious to increase the number of monthly loading doses from three to five.
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`To the contrary, doctors were motivated to decrease the number of injections to
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`reduce the treatment burden on patients, not to increase them.
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`Fourth, Samsung’s alternative argument in Grounds X and XI, that the
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`results limitations lack patentable weight, also fails. As the Board has now held
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`twice, the results limitations constrain what methods practice the claims.
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`II. BACKGROUND
`A. EYLEA®
`In 2011, the FDA approved aflibercept, under the brand name Eylea®, for
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`treatment of wAMD. (Ex.2001, ¶64.) Approval for another angiogenic eye
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`disorder, DME, followed in 2014. (Id., ¶67.) Despite debuting five years after
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`other anti-VEGF agents, Eylea® is now the anti-VEGF therapy most commonly
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`used for both wAMD and DME. (Id., ¶¶64-67, 69.) Its popularity is largely due to
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`a dosing regimen that allows for less frequent maintenance dosing compared to
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`other anti-VEGF options while halting disease progression and yielding visual
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`acuity gains. (Id., ¶¶29, 86-89, 93.) Unlike Genentech’s Lucentis®, whose label
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`requires monthly administration for wAMD and DME, Eylea® can be
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`administered on a fixed, every-eight-week schedule. (Id., ¶¶40-41.) This “q8”
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`maintenance dosing follows an initial “primary” dose and a number of monthly
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`“secondary” doses. (Ex.2002, §§ 2.2, 2.4.)
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`1.
`Development of Eylea® for AMD
`Dr. George Yancopoulos, Regeneron’s co-founder, President, and Chief
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`Scientific Officer, had the idea to use one initial dose, followed by two secondary
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`doses every four weeks, and then followed by tertiary doses every eight weeks.
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`Dr. Yancopoulos directed Phase III VIEW clinical trials to test the efficacy of this
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`regimen. (Ex.2063, ¶¶16-25, 28; Ex.2064, ¶¶21-22.)
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`The VIEW trials followed Regeneron’s Phase I and II trials, called CLEAR-
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`IT-1 and CLEAR-IT-2, respectively. (Ex.1009, 3-4.) CLEAR-IT-1 and CLEAR-
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`IT-2 used investigatory dosing regimens significantly different from what the
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`Eylea® label would eventually recommend. (Compare Ex.1009, 3-4 with Ex.2002
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`and Ex.2003, 137:22-24.)2 For CLEAR-IT-1, each of 21 subjects received a single
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`injection of 0.05 to 4mg. (Ex.1027.) For CLEAR-IT-2, Regeneron tested dose
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`amounts from 0.5 to 4mg. (Ex.1009, 4.) In the first 12 weeks, subjects received
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`injections either monthly or quarterly. (Id.) Then, all subjects were treated on a
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`PRN (as-needed) basis. (Id.) Regeneron and Dr. Yancopoulos obtained positive
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`interim results from CLEAR-IT-2 in late March 2007. (Ex.2063, ¶19; Ex.2064,
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`¶17; Exs.2004-2006.)
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`By March 2007, Dr. Yancopoulos had the idea to test a dosing regimen of
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`three loading doses administered every four weeks (an initial dose and two
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`secondary doses) followed by doses every eight weeks (the “q8” dosing regimen).
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`(Ex.2063, ¶¶16-22; Ex.2064, ¶21.) With the knowledge that Lucentis® did not last
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`two months—in the two months after an injection, patients would gain and then
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`lose vision before the next injection, (Ex.2063, ¶18; Ex.2003, 131:5-23, 137:7-21;
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`2 Citations to Ex.2003 use the transcript’s original page and line numbers.
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`Ex.2007, 46-47)—he hoped that aflibercept could achieve lasting gains when
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`dosed every two months, (Ex.2063, ¶25; Ex.2003, 131:24-132:5.). This less-
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`frequent dosing would, in Dr. Yancopoulos’s words, “halve the treatment burden”
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`and “provide a major advance.” (Ex.2003, 132:2-4.)
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`Dr. Yancopoulos initially decided to pair this eight-week dosing with three
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`monthly loading doses. (Ex.2063, ¶¶20-23; compare Exs.2073-2074 with
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`Exs.2070-2072.) He decided that the highest dose tested in the VIEW trials would
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`be 2mg because the benefits of using a 4mg dose were not clear, and there was also
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`concern of an increased risk of toxicities at a higher dose. (Ex.2063, ¶24; Ex.2009;
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`Ex.2075, 1.) He also made the final decision to proceed with the VIEW trial
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`design, which included his q8 dosing regimen, monthly dosing of 0.5mg and 2mg
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`of aflibercept, and a comparator arm of monthly Lucentis®. (Ex.2063, ¶28;
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`Ex.2064, ¶¶21-23; Ex.2076, 2.)
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`Executing on Dr. Yancopoulos’s idea, Regeneron and its commercial partner
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`Bayer carried out the VIEW trials. (Ex.2063, ¶30; Ex.2064, ¶24; Ex.1005.)
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`Regeneron announced in September 2009 that it had completed enrollment of the
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`VIEW trials, and the last patient completed 52 weeks of treatment in September
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`2010. (Ex.1005; Ex.1038, 3.) On November 19 and 20, 2010, Dr. Yancopoulos
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`received the VIEW results and recognized that his q8 dosing regimen had worked.
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`(Ex.2063, ¶¶32-34; Ex.2010; Ex.2011, 4-6.) The results included the following
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`charts, which show the 2q8 regimen both improved vision compared to baseline
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`and was non-inferior to monthly 0.5mg Lucentis ® (ranibizumab):
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`(Ex.2043, 6.)
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`c 2-o
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`(Ex.2043, 5.)
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`*Statistically
`non-inferior
`vs. Rq4
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`VIEW 1 + VIEW 2
`Primary Endpoint: Maintenanceof Vision
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`7 LOCF; per protocol set; Rq4 n=538; 2q4 n=559; 0.5q4 n=538; 2q8 n=535
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`a
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`96.1%" 0.5q4
`95.3%" 204
`95.3%" 2q8
`94.4% Rad
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`(Ex.2011, 4.)
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`On November 22, 2010, Regeneron published the top-line VIEW results in
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`the November 2010 PR. (Ex.2063, ¶35; Ex.1007).
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`2.
`Development of Eylea® for DME
`After starting the VIEW trial, Regeneron began testing the same q8 dosing
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`regimen for DME patients in its Phase II DA VINCI trial. (Ex.2063, ¶¶36-38;
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`Ex.2064, ¶¶29-31.) By mid-2008, Regeneron had selected five treatment arms for
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`its DA VINCI trial, including a q8 arm as in VIEW. (Compare Ex.2013 with
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`Ex.1006 and Ex.1007.) DA VINCI included a primary visual acuity endpoint at
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`24 weeks and a secondary visual acuity endpoint at 52 weeks. (Ex.2015, 3.)
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`The 24-week results in DA VINCI became available within Regeneron by
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`early 2010. (Ex.2063, ¶40; Exs.2017-2019.) Dr. Yancopoulos received these
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`results on February 1, 2010, at which time he recognized that his 2q8 regimen
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`yielded an improvement of 9 or more letters in some patients with DME as
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`compared to baseline at 24 weeks:
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`(Ex.2019, 13; Ex.2063, ¶¶40-41; Exs.2017-2019.)
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`On February 18, 2010, Regeneron published the top-line 24-week DA
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`VINCI results in a press release. (Ex.2020.) Regeneron then presented these
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`results at the 2010 meeting of the Association for Research in Vision and
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`Ophthalmology (ARVO). (Ex.2064, ¶¶41-42; Ex.2066, ¶40.) It provided an
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`abstract summarizing the 24-week results to Drs. David Brown and James Major,
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`who submitted it to the 2010 ARVO meeting. (Ex.2066, ¶¶42-45; Ex.2021;
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`compare Ex.2022 with Ex.1010.)
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`Regeneron began planning its Phase III DME trial after receiving the 24-
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`week DA VINCI results. By October 2010, Regeneron planned to test the q8
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`regimen that it had used in the DA VINCI trial, (Ex.2003, 162:7-9, 1616:19-25),
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`but it awaited the DA VINCI 52-week data to “provide additional guidance on the
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`number of loading doses.” (Id., 162:10-163:3.)
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`Regeneron completed the DA VINCI trial and, on December 8, 2010,
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`Dr. Yancopoulos received the one-year results. (Ex.2063, ¶¶45-46; Ex.2015;
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`Ex.2024.) The results confirmed that the 24-week visual acuity gains could be
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`sustained over time using the 2q8 regimen:
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` (Ex.2063, ¶46; Ex.2015, 11.)
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`On December 20, 2010, Regeneron reported the top-line one-year DA
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`VINCI results in the December 2010 PR. (Ex.2063, ¶47; Ex.1006.) Then, after
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`reviewing the 52-week data, Dr. Yancopoulos made the decision to test five
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`loading doses, one “initial” dose and four “secondary doses,” followed by q8
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`dosing in the Phase III DME trial. (Ex.2003, 1622:15-1623:14, 1234:8-1235:4,
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`167:25-168:22.)
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`3.
`Eylea®’s Commercial Success
`Following FDA approval, Eylea® was an immediate success. By 2012,
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`Eylea®’s share of sales across all indications was
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`. (Ex.2067, ¶20, [C-6].) By
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`2021, that figure had
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`. (Id.) Today, Eylea® has the highest
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`market share among anti-VEGF products for the treatment of both DME and
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`wAMD. (Ex.2067, ¶¶22, 24, [C-7, C-9].) It also ranks as the top preference for a
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`majority of physicians compared to other anti-VEGF treatments. (Ex.2067, ¶30,
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`[E-1].) That is due in large part to its q8 dosing regimen, which is effective with
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`fewer painful injections into the eye than other treatments. (Ex.2067, ¶¶38-39, [E-
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`3]; [E-4]; Ex.2143, 46; Ex.2144, 94.)
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`B.
`’572 Patent
`The ’572 Patent discloses and claims eight-week extended dosing regimens
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`for aflibercept and the successes achieved while using it. It addresses a “need in
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`the art for new administration regimens for angiogenic eye disorders, especially
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`those which allow for less frequent dosing while maintaining a high level of
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`efficacy.” (Ex.1001, 2:6-9.) All but three claims require not only a particular
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`dosing regimen, but also achieving certain visual acuity results.
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`The ’572 Patent claims priority to provisional application No. 61/432,245,
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`filed on January 13, 2011, shortly after Regeneron received the critical one-year
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`results of the VIEW and DA VINCI trials. (Ex.1001.) The provisional application
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`reports both the trial protocols and results for the VIEW and DA VINCI trials.
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`(See Ex.2145, ¶¶58-60 (VIEW), ¶¶61-62 (DA VINCI); Ex.1001, 13:10-27
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`(VIEW), 14:32-15:12 (DA VINCI).)
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`III. PRIORITY DATE
`Consistent with the Board’s DI, all claims of the ’572 Patent are entitled to a
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`priority date no later than January 13, 2011. (DI, 30-34.) Samsung challenges that
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`date for only one claim, contending that Regeneron did not disclose claim 25’s
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`subject matter—four secondary doses—before July 12, 2013. But Regeneron’s
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`January 13, 2011 provisional discloses exactly that: “In other embodiments, two or
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`more (e.g., 2, 3, 4, 5, 6, 7, 8, or more) secondary doses are administered to the
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`patient.” (Ex.2145 ¶18; Ex.1001, 4:26-28.) So does Regeneron’s January 21,
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`2011 provisional. (Ex.2025, ¶18.) And if that were not enough—it is—both
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`provisionals point the reader to the lower end of that disclosed range. (Ex.2145, ¶5
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`(“about three doses”); Ex.2025, ¶5 (same).) Claim 25 thus has a January 2011
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`priority date. (DI, 33.) See Snitzer v. Etzel, 465 F.2d 899, 902 (CCPA 1972)
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`(“[T]here would seem to be little doubt that the literal description of a species
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`provides the requisite legal foundation for claiming that species.”); Ariad Pharms.,
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`Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010).
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`Samsung’s Petition identifies no reason why the foregoing disclosures are
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`insufficient. In Samsung’s two-paragraph argument (Pet. 14) it merely cross
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`references nine paragraphs of its expert Dr. Chaum’s testimony (Ex.1002, ¶¶91-
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`103). But that opinion deserves no weight. Dr. Chaum conducted no analysis of
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`the priority dates of the claims. (Ex.2090, 325:9-12.) When asked how he reached
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`his opinion, Dr. Chaum testified that July 12, 2013 was just “the date that I have
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`been asked to assume.” (Id., 324:11-12.) In a related proceeding involving similar
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`claims, Dr. Chaum admitted he “did not know the requirements” for what
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`disclosure is required to obtain a patent (Ex.2062, 40:13-22), and that he had not
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`reviewed any provisional applications in reaching his opinion regarding the
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`priority date. (Id., 154:4-22.)
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`The ’572 Patent thus has a priority date of January 13, 2011, and is subject
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`to the first-to-invent provisions of pre-AIA 35 U.S.C. §§ 102 and 103. See MPEP
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`§ 2159.3
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`IV. LEVEL OF ORDINARY SKILL IN THE ART
`For purposes of this IPR, Regeneron does not contest Samsung’s proposed
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`definition of a person of ordinary skill. (Pet. 14-15.)
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`3 Even if AIA standards were applicable, Samsung has not shown that any of the
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`challenged claims are unpatentable.
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`V. CLAIM CONSTRUCTION
`A. The Results Limitations Have Patentable Weight (all claims)
`As the Board has now found twice, the results limitations have patentable
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`weight because they constrain the claims. (DI, 21-30; Ex.1004, 18.) Specifically,
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`they “inform the reader about the purpose of the methods (or ‘the essence of the
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`invention’), which, for most claims, is to gain or maintain visual acuity, and also
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`illuminate the dosage administration steps in a material way, i.e., so that one may
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`know collectively how many secondary or tertiary doses are sufficient.” (DI, 27.)
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`The Board thus should again follow LA Biomed v. Eli Lilly and confirm
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`patentable weight. 849 F.3d 1049, 1061 (Fed. Cir. 2017). There, an efficacy
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`limitation had patentable weight because it narrowed the claims covering a variable
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`dosing regimen to instances where that regimen worked. Id. at 1061. Here too, the
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`results limitations require achieving listed gains in visual acuity and that the
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`number of secondary and tertiary doses administered be sufficient to yield those
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`gains. (See DI, 25, 27.) “[T]he results limitations … must be given patentable
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`weight for the same reasons as … in Los Angeles Biomed.” (DI, 30.)
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`Samsung’s arguments to the contrary should again be rejected. As an initial
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`matter, Samsung is wrong to treat the results limitations as lesser because they
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`appear in “wherein” clauses—“wherein” limitations can and do have patentable
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`weight where, as here, they give meaning and purpose to the manipulative steps of
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`the claims. (DI, 27). In re Kubin is not to the contrary; it is simply a case about an
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`application where one particular “wherein” limitation was, according to the
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`specification, not a requirement. 561 F.3d 1351, 1357 (Fed. Cir. 2009). As the
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`Board noted, “[t]he active steps of every independent claim of the ’572 patent are
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`styled as ‘wherein’ clauses,” and not even Samsung advocates for ignoring those
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`steps. (DI, 27.) Moreover, ignoring the results limitations would improperly
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`collapse the distinctions between dependent claims. (Ex.1001 (compare claims 3
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`and 8 with claim 2, where only difference in scope is the results limitations));
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`Comark Comm’ns, Inc. v. Harris Corp., 156 F.3d 1182, 1187 (Fed. Cir. 1998)
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`(presumption of claim differentiation).
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`The Board also should reject Samsung’s second affirmative argument, which
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`analogizes to some cases where claim limitations directed to intended or inherent
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`results were found to lack patentable weight. (Pet. 57-60.) As the Board
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`previously found, the results limitations “are not mere intended results that
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`inherently occur.” (DI, 28; see also Ex.1004, 34.) In a 52-week clinical trial
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`involving AMD, for example, the claimed, 2q8 regimen yielded no benefits to
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`visual acuity in at least 4-5% of patients. (Ex.1001, 13:7-28.) A shorter clinical
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`trial involving DME was similar. (Ex.1031, 4 (~7% of 2q8 group gained no
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`letters).) Thus, Syntex, Bristol-Myers, Copaxone, Kubin, Lockheed Martin, and
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`Minton—all cases involving limitations covering intended results or inherent
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`outcomes—are inapposite.
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`Samsung’s reliance on the Mylan claim construction order is also misplaced.
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`(Pet. 19.) That order “overlooked [the] critical fact[]” that the claimed, 2q8
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`regimen is “variable and necessarily informed” by the results limitations, and the
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`authorities on which it rests are therefore “factually distinguishable.” (DI, 29;
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`Ex.1063, 37-39.) As the Board previously recognized, it “is not bound” by the
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`Mylan court’s construction, and it should not follow it here. (DI, 28.)
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`B.
`“A method of treating”4 (all claims)
`Each independent claim requires “[a] method of treating” an “angiogenic
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`eye disorder,” “diabetic macular edema,” or “age[-]related macular degeneration.”
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`(Ex.1001, (claims 1, 15, 26, 29).) As at institution, the Board should find that this
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`term requires at least an intent to treat the recited diseases. (DI, 20.) The parties
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`agree on this construction, and it matches the Board’s treatment of similar terms in
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`related patents. (Pet. 17-18; see Ex.1011, 19; Ex.1013, 9-10.)
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`4 Solely for the purposes of this Response, Regeneron applies Samsung and the
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`Board’s claim construction throughout this Response.
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`C.
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`“approximately 4 weeks following the immediately preceding dose
`. . . approximately 8 weeks following the immediately preceding
`dose” (claims 1, 15 26, 29)
`The customary meanings of these terms require dosing aflibercept at
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`predetermined, fixed intervals. (Ex.2065, ¶¶64-74.) These terms expressly require
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`dosing at intervals of “approximately 4 weeks” and “approximately 8 weeks.”
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`(Ex.1001, (claims 1, 15, 26, 29); Ex.2065, ¶67.) And they make no m