`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`
`SAMSUNG BIOEPIS CO., LTD.,
`Petitioner,
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`
`Patent No. 11,253,572
`_______________
`
`
`
`Inter Partes Review No. IPR2023-00884
`____________________________________________________________
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`
`
`
`
`
`
`
`Biocon Exhibit 1067 Page 1
`
`

`

`IPR2023-00884
`
`TABLE OF CONTENTS
`
`Page
`
`I.
`II.
`
`III.
`IV.
`V.
`
`VI.
`
`INTRODUCTION .......................................................................................... 1
`BACKGROUND ............................................................................................ 3
`A.
`EYLEA® .............................................................................................. 3
`1.
`Development of Eylea® for AMD ............................................ 4
`2.
`Development of Eylea® for DME ............................................. 6
`’572 Patent ............................................................................................ 7
`B.
`Apotex Petition ..................................................................................... 8
`C.
`District Court Litigation ..................................................................... 10
`D.
`PRIORITY DATE ........................................................................................ 12
`LEVEL OF ORDINARY SKILL IN THE ART .......................................... 13
`CLAIM CONSTRUCTION ......................................................................... 13
`A.
`The Results Limitations Have Patentable Weight .............................. 14
`THE BOARD SHOULD DENY INSTITUTION BECAUSE
`PETITIONER HAS NO REASONABLE LIKELIHOOD OF
`SUCCESS ON ANY GROUND .................................................................. 20
`A.
`Ground II: The December 2010 Press Release Is Not Prior Art ....... 22
`1.
`The Invention Was Conceived and Reduced to Practice
`Before December 20, 2010 ...................................................... 22
`The December 2010 Press Release Discloses the
`Inventor’s Own Work .............................................................. 25
`Ground III: The November 2010 Press Release Is Not Prior Art ..... 26
`1.
`The Invention Was Conceived and Reduced to Practice
`Before November 22, 2010 ...................................................... 26
`The November 2010 Press Release Discloses the
`Inventor’s Own Work .............................................................. 27
`Ground IV: Dixon and the 2006 Press Release Do Not Disclose
`the Visual Acuity Results ................................................................... 28
`Ground V ............................................................................................ 38
`
`B.
`
`C.
`
`D.
`
`2.
`
`2.
`
`-i-
`
`Biocon Exhibit 1067 Page 2
`
`

`

`IPR2023-00884
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`1.
`
`E.
`
`F.
`
`The 2009 Press Release, Dixon, and 2007 ARVO
`Abstract Do Not Disclose the Visual Acuity Results .............. 39
`The 2010 ARVO Abstract Is Not Prior Art ............................. 40
`2.
`Ground VI ........................................................................................... 42
`1.
`Dixon and the 2006 Press Release Do Not Disclose the
`Visual Acuity Results .............................................................. 42
`The December 2010 Press Release Is Not Prior Art ................ 42
`2.
`Ground VII ......................................................................................... 43
`1.
`The 2009 Press Release, Dixon, and 2007 ARVO
`Abstract Do Not Disclose the Visual Acuity Results .............. 43
`The 2010 ARVO Abstract Is Not Prior Art ............................. 43
`2.
`The December 2010 Press Release Is Not Prior Art ................ 43
`3.
`Ground VIII ........................................................................................ 44
`1.
`Dixon Does Not Disclose the Visual Acuity Results .............. 44
`2.
`The December 2010 Press Release Is Not Prior Art ................ 44
`Ground IX: The 2009 Press Release, Shams, and Elman 2010
`Do Not Disclose Four Secondary Doses ............................................ 44
`Ground X: The Results Limitations Have Patentable Weight .......... 47
`Ground XI: The Results Limitations Have Patentable Weight ......... 47
`Ground I: The 2009 Press Release Does Not Disclose that the
`VEGF Antagonist Was Administered for the Purpose of
`Treating an Angiogenic Eye Disorder ................................................ 48
`VII. THE BOARD SHOULD DENY INSTITUTION UNDER FINTIV
`BECAUSE THE SAME CLAIMS AND ART ARE AT ISSUE IN
`DISTRICT COURT ...................................................................................... 49
`A.
`Fintiv Factors One, Two, Three, Four, and Six Favor Denial ........... 50
`B.
`Fintiv Factor Five Does Not Outweigh the Other Fintiv Factors ...... 53
`
`G.
`
`H.
`
`I.
`J.
`K.
`
`-ii-
`
`Biocon Exhibit 1067 Page 3
`
`

`

`IPR2023-00884
`
`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`VIII. THE BOARD SHOULD DENY INSTITUTION UNDER 35 U.S.C.
`§ 325(D) BECAUSE THE EXAMINER AND BOARD REJECTED
`THE SAME ART AND ARGUMENTS ...................................................... 54
`A.
`The Board Considered and Rejected the Art and Arguments ............ 55
`B.
`The Examiner Allowed the ’572 Patent After Considering the
`Asserted Art ........................................................................................ 58
`C. No Material Error ............................................................................... 61
`
`
`
`
`
`
`
`-iii-
`
`
`
`Biocon Exhibit 1067 Page 4
`
`

`

`IPR2023-00884
`
`Cases
`
`TABLE OF AUTHORITIES
`
`
`
`Page(s)
`
`Advanced Bionics, LLC v. MED-EL Elektromedizinische
`Geräte GmbH,
`IPR2019-01469, 2020 WL 740292 (P.T.A.B. Feb. 13, 2020) ......... 55, 56, 58, 61
`
`Allergan Sales, LLC v. Sandoz, Inc.,
`935 F.3d 1379 (Fed. Cir. 2019) ........................................................ 14, 15, 18, 19
`
`Apotex Inc. v. Regeneron Pharmaceuticals, Inc.,
`IPR2022-01524, Paper 9 (P.T.A.B. Mar. 10, 2023) ....................................passim
`
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019, 2020 WL 2126495 (P.T.A.B. Mar. 20, 2020) ..................passim
`
`Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co.,
`598 F.3d 1336 (Fed. Cir. 2010) .......................................................................... 13
`
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, 2017 WL 6405100 (P.T.A.B. Dec. 15, 2017) ................... 55, 62
`
`In re Best,
`562 F.2d 1252 (C.C.P.A. 1977) .......................................................................... 34
`
`Bristol-Myers Squibb v. Ben Venue Lab’ys, Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) .................................................................... 16, 17
`
`Comark Comm’ns, Inc. v. Harris Corp.,
`156 F.3d 1182 (Fed. Cir. 1998) .......................................................................... 18
`
`Commscope Techs. LLC v. Dali Wireless, Inc.,
`IPR2022-01293, 2023 WL 2604001 (P.T.A.B. Mar. 9, 2023) ........................... 51
`
`Fitbit, Inc. v. Philips N. Am. LLC,
`IPR2020-00828, 2020 WL 6470312 (P.T.A.B. Nov. 3, 2020)........................... 54
`
`Foundation Medicine, Inc. v. Guardant Health, Inc.,
`IPR2019-00636, Paper 10, 13 (P.T.A.B. Aug. 20, 2019) ................................... 34
`
`
`
`i
`
`Biocon Exhibit 1067 Page 5
`
`

`

`IPR2023-00884
`
`
`
`
`
`Gilead Scis., Inc. v. United States,
`IPR2019-01456, 2020 WL 582217, (P.T.A.B. Feb. 5, 2020) ................ 16, 19, 31
`
`Google LLC v. Personalized Media Comms., LLC,
`IPR2020-00724, 2020 WL 6530785 (P.T.A.B. Nov. 5, 2020)........................... 54
`
`Griffin v. Bertina,
`285 F.3d 1029 (Fed. Cir. 2002) .......................................................................... 14
`
`Husky Injection Molding Sys., Ltd. v. Plastipak Packaging, Inc.,
`IPR2020-00431, Paper 23 (P.T.A.B. July 28, 2020) .......................................... 58
`
`In re Copaxone 40 Mg, No. CV 14-1171-GMS, 2016 WL 873062, (D.
`Del. Mar. 7, 2016) ............................................................................................... 16
`
`Jones v. Hardy,
`727 F.2d 1524 (Fed. Cir. 1984) .......................................................................... 18
`
`In re Katz,
`687 F.2d 450 (C.C.P.A. 1982) ............................................................................ 25
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 45
`
`L’Oréal USA, Inc. v. Olaplex, Inc.,
`844 F. App’x 308 (Fed. Cir. 2021) ..................................................................... 17
`
`Lockheed Martin Corp. v. Space Sys./Loral, Inc.,
`324 F.3d 1308 (Fed. Cir. 2003) .......................................................................... 15
`
`Los Angeles Biomedical Research Institute at Harbor-UCLA Medical
`Center v. Eli Lilly & Co.,
`849 F.3d 1049 (Fed. Cir. 2017) ...................................................................passim
`
`Microsoft Corp. v. IPA Techs. Inc.,
`IPR2019-00839, 2019 WL 5860714 (P.T.A.B Nov. 8, 2019)............................ 60
`
`Minton v. Nat’l Ass’n of Sec. Dealers, Inc.,
`336 F.3d 1373 (Fed. Cir. 2003) .......................................................................... 17
`
`Newkirk v. Lulejian,
`825 F.2d 1581 (Fed.Cir.1987) ............................................................................ 24
`
`
`
`ii
`
`Biocon Exhibit 1067 Page 6
`
`

`

`IPR2023-00884
`
`
`
`
`
`NHK Spring Co. v. Intri-Plex Techs., Inc.,
`IPR2018-00752, Paper 8, 20 (P.T.A.B. Sept. 12, 2018) .................................... 50
`
`Palo Alto Networks, Inc. v. Centripetal Networks, Inc.,
`IPR2021-01520, 2022 WL 945569 (P.T.A.B. Mar. 22, 2022) ........................... 56
`
`PAR Pharm., Inc. v. TWI Pharms., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) ........................................................ 31, 33, 35, 40
`
`Portney v. CIBA Vision Corp.,
`401 F. App’x 526 (Fed. Cir. 2010) ..................................................................... 11
`
`Samsung Electronics. Co. v. Clear Imaging Research., LLC,
`IPR2020-01399, Paper 13 (P.T.A.B. Feb. 3, 2021) ............................................ 53
`
`Snitzer v. Etzel,
`465 F.2d 899 (CCPA 1972) ................................................................................ 12
`
`Syntex (U.S.A.) LLC v. Apotex, Inc.,
`407 F.3d 1371 (Fed. Cir. 2005) .......................................................................... 17
`
`Townsend v. Smith,
`36 F.2d 292 (CCPA 1929) ............................................................................ 23, 27
`
`Volvo Penta of the Ams., LLC v. Brunswick Corp.,
`IPR2022-01366, Paper 15 (P.T.A.B. May 2, 2023) ........................................... 50
`
`Statutes
`
`35 U.S.C. § 102 .................................................................................................passim
`
`Other Authorities
`
`MPEP § 717.01(a)(1) ................................................................................... 25, 27, 41
`
`MPEP § 2159 ........................................................................................................... 13
`
`
`
`
`
`iii
`
`Biocon Exhibit 1067 Page 7
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`Exhibit List
`
`Exhibit Description
`
`2001
`
`2002
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`2012
`
`2013
`
`Expert Declaration of Richard Manning, Ph.D., Mylan Pharms.
`Inc. v. Regeneron Pharms., Inc., IPR2021-00881, Ex. No. 2052
`(Feb. 11, 2022)
`EYLEA® Label (rev. Oct. 2014)
`Trial Transcript (unsealed portions), Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.)
`Press Release, Positive Interim Phase 2 Data Reported for VEGF
`Trap-Eye in Age-Related Macular Degeneration, Regeneron
`Pharmaceuticals, Inc. (Mar. 27, 2007)
`Email from George Yancopoulos to Murray Goldberg re Top Line
`sum for PR (Mar. 22, 2007)
`Interim Analysis of Phase 2 Study of VEGF Trap in AMD patients
`(Mar. 22, 2007) (Attachment to Ex.2005)
`George D. Yancopoulos, VEGF Trap : Scientific Background,
`BSP / REGN Kick-Off (Feb. 16, 2007)
`Email from Kathleen Lawrence re Decisions & Actions: AMD
`Ph3 Program Mtg – 4/2/07 (Apr. 2, 2007)
`Email from George Yancopoulos to Darlene Jody re Summary of
`issues for call: AMD P3 Planning with enclosed outline attached
`(Apr. 4, 2007)
`Email from Robert Terifay to George Yancopoulos re VGTeye
`VIEW 430 presentation (Nov. 19, 2010)
`Vascular Endothelial Growth Factor (VEGF) Trap-Eye:
`Investigation of Efficacy and Safety in Wet Age-Related Macular
`Degeneration (AMD) - VIEW 1 and VIEW 2 – 1-Year Results
`(Attachment to Ex.2010)
`Regeneron Pharmaceuticals, Phase 1 Study of VEFT Trap in
`Patients With Diabetic Macular Edema,
`https://clinicaltrials.gov/study/NCT00320814 (last updated Jun.
`10, 2011)
`Regeneron, Clinical Study Concept - Ophthalmology-Diabetic
`Macular Edema-Phase 2-IVT-VGFT-OD-0706 (updated May 19,
`2008)
`
`
`
`iv
`
`Biocon Exhibit 1067 Page 8
`
`

`

`IPR2023-00884
`
`
`
`
`
`Exhibit No.
`
`Exhibit Description
`
`2014
`
`2015
`
`2016
`
`2017
`2018
`
`2019
`
`2020
`
`2021
`
`2022
`
`2023
`
`2024
`
`2025
`
`2026
`
`2027
`
`Diana V. Do et al., One-Year Outcomes of the DA VINCI Study of
`VEGF Trap-Eye in Eyes with Diabetic Macular Edema, 119
`OPHTHALMOLOGY 1658-1665 (Aug. 2012).
`DA VINCI – DME And VEGF Trap-Eye: Investigation of Clinical
`Impact: One Year Data (Dec. 8, 2010) (attachment to Ex.2024)
`Regeneron Pharmaceuticals, DME And VEGF Trap-Eye
`[Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)]
`INvestigation of Clinical Impact (DA VINCI),
`https://clinicaltrials.gov/study/NCT00789477 (last updated Sep. 9,
`2014)
`Email from Caroline Saxton re Data Review (Feb. 1, 2010)
`Regeneron Pharmaceuticals, Inc., VGFT-OD-0706 Week 24
`Topline Results (Feb. 1, 2010) (attachment to Ex.2017)
`DRAFT – DA VINCI – 6-Month Primary Endpoint (Feb. 1, 2010)
`(attachment to Ex.2017)
`Regeneron Pharmaceuticals, Inc., VEGF Trap-Eye Shows Positive
`Results in a Phase 2 Study in Patients With Diabetic Macular
`Edema (Feb. 18, 2010)
`Email from Alyson Berliner to Dave Brown re ARVO late
`breakers (Mar. 1, 2010)
`DA VINCI: DME And VEGF Trap-Eye: Investigation of Clinical
`Impact: Phase 2 study in patients with Diabetic Macular Edema
`(DME) (Mar. 1, 2010) (Attachment to Ex.2021)
`Email from Dave Brown to Alyson Berliner and James Major re
`ARVO abstract (Mar. 3, 2010)
`Email from Caroline Saxton re Slides and tables – DaVinci (Dec.
`8, 2010)
`U.S. Provisional Patent Application No. 61/434,836 (Jan. 21,
`2011)
`Mylan Pharmaceuticals Inc.’s Answer, Defenses, and
`Counterclaims to Plaintiff's Complaint, Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.),
`ECF No. 47 (filed Aug. 25, 2022)
`Stipulation and Order Joining Biocon Biologics Inc. as Defendant,
`Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No. 1:22-cv-
`00061-TSK-JPM (N.D.W. Va.), ECF No. 523 (filed Jun. 5, 2023)
`
`
`
`v
`
`Biocon Exhibit 1067 Page 9
`
`

`

`IPR2023-00884
`
`
`
`
`
`Exhibit No.
`
`Exhibit Description
`
`2028
`
`2029
`
`2030
`
`2031
`
`2032
`
`2033
`
`2034
`
`2035
`
`2036
`2037
`
`2038
`
`2039
`
`2040
`
`Complaint for Patent Infringement, Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.),
`ECF No. 1 (filed Aug. 2, 2022)
`Order on Claim Construction, Regeneron Pharms., Inc. v. Mylan
`Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF
`No. 427 (filed Apr. 19, 2023)
`Scheduling Order, Regeneron Pharms., Inc. v. Mylan Pharms.
`Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF No. 87
`(filed Oct. 25, 2022)
`Regeneron's Stipulation Regarding Summary Judgment and Case
`Narrowing, Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No.
`1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF No. 433 (filed Apr.
`27, 2023)
`Defendant's Opening Post Trial Brief - Issues Where Defendants
`Bear the Burden of Proof, Regeneron Pharms., Inc. v. Mylan
`Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF
`No. 576 (filed July 7, 2023)
`Order Setting Briefing Schedule, Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.),
`ECF No. 514 (filed May 30, 2023)
`Transcript of the Status Conference held on Sept. 28, 2022,
`Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No. 1:22-cv-
`00061-TSK-JPM (N.D.W. Va.), ECF No. 90 (filed Nov. 2, 2022)
`Email from George Yancopoulos re DME Phase 2 – ALL
`TABLES (Feb. 2, 2010)
`DME Target Product Profile - VEGF Trap-Eye (Sept. 26, 2007)
`Clinical Development & Regulatory Affairs Weekly Update (Oct.
`29, 2010)
`Clinical Development & Regulatory Affairs Weekly Update (Dec.
`3, 2010)
`Email from George Yancopoulos re DME PLANS & FDA
`meeting pre-discussion (Jan. 9, 2008)
`MEMO re Guidance From Bayer/ REGN Sr. Management
`Regarding Additional Indications in Ophthalmology from George
`Yancopoulos to Bayer/REGN Joint Development Group (Mar. 28,
`2008)
`
`
`
`vi
`
`Biocon Exhibit 1067 Page 10
`
`

`

`IPR2023-00884
`
`
`
`
`
`Exhibit No.
`
`Exhibit Description
`
`2041
`
`2042
`
`2043
`
`2044
`
`2045
`
`2046
`
`2047
`
`2048
`
`2049
`
`2050
`
`2051
`
`Action Items by GD Yancopoulos - Bayer/REGN JSC (Feb. 15,
`2008)
`Email from Yuhwen Soo to George Yancopoulos re Can you send
`me that slide you made combining the VA curves for View1 &
`View2 (Nov. 20, 2010)
`Vascular Endothelial Growth Factor (VEGF): Investigation of
`Efficacy and Safety in Wet Age-Related Macular Degeneration
`(AMD)—VIEW1 + VIEW 2: 1-Year Results (Nov. 20, 2010)
`(Attachment to Ex.2042)
`Email from Michael Aberman to George Yancopoulos and
`Leonard Schleifer re Press Release (Nov. 19, 2010)
`Regeneron, Bayer and Regeneron Report Positive Top-Line
`Results of Two Phase 3 Studies with VEGF Trap-Eye in Wet Age-
`related Macular Degeneration (Nov. 19, 2010) (Attachment to
`Ex.2044)
`U.S. Food & Drug Administration, 22 Case Studies Where Phase
`2 and Phase 3 Trials Had Divergent Results (Jan. 2017)
`VEGF Trap-Eye in Wet AMD - CLEAR-IT 2: Summary of One-
`Year Key Results, Presented at 2008 Retina Society Meeting,
`Scottsdale, Arizona (Sep. 28, 2008)
`Regeneron Pharmaceuticals, Inc., A Double-Masked, Randomized,
`Controlled Study of the Safety, Tolerability and Biological Effect
`of Repeated Intravitreal Administration of VEGF Trap-Eye in
`Patients with Diabetic Macular Edema (DME) (Issued Jan. 28,
`2009)
`Appendix to Heier et al., Intravitreal Aflibercept (VEGF Trap-
`Eye) in Wet Age-Related Macular Degeneration, 119
`OPHTHALMOLOGY 2537 (2012)
`Retinal Physician Symposium Covers Broad Range of Topics,
`Retinal Physician (Sept. 1, 2006),
`https://www.retinalphysician.com/issues/2006/september2006/reti
`nal-physician-symposium-covers-broad-range-of
`Prema Abraham et al., Randomized, Double-Masked,
`ShamControlled Trial of Ranibizumab for Neovascular Age-
`Related Macular Degeneration: PIER Study Year 2, 150 AM. J.
`OPHTHALMOLOGY 315 (2010)
`
`
`
`vii
`
`Biocon Exhibit 1067 Page 11
`
`

`

`IPR2023-00884
`
`
`
`
`
`Exhibit No.
`
`Exhibit Description
`
`2052
`
`2053
`2054
`
`2055
`
`2056
`
`2057
`
`2058
`
`2059
`
`FDA, Step 3: Clinical Research,
`https://www.fda.gov/patients/drug-development-process/step-3-
`clinical-research (last accessed Aug. 23, 2023)
`Prosecution History of U.S. Patent App. No. 16/159,282 B2
`Anant Pai et al., Current concepts in intravitreal drug therapy for
`diabetic retinopathy, 24 SAUDI J. OPHTHALMOLOGY 143 (June 30,
`2010)
`David M. Brown et al., Long-term Outcomes of Ranibizumab
`Therapy for Diabetic Macular Edema: The 36-Month Results from
`Two phase Ill Trials, 120 OPHTHALMOLOGY 2013 (2013)
`Jean-Francois Korobelnik et al., Intravitreal Aflibercept for
`Diabetic Macular Edema, 121 OPHTHALMOLOGY 2247 (2014)
`Quan Dong Nguyen et al., Ranibizumab for Diabetic Macular
`Edema, Results from 2 Phase Ill Randomized Trials: RISE and
`RIDE, 119 OPHTHALMOLOGY 789 (2012)
`Ursula Schmidt-Erfurth et al., Three-Year Outcomes of
`Individualized Ranibizumab Treatment in Patients with Diabetic
`Macular Edema. 121 OPHTHALMOLOGY 1045 (2014)
`Default Protective Order
`
`
`
`
`
`
`
`viii
`
`Biocon Exhibit 1067 Page 12
`
`

`

`IPR2023-00884
`
`I.
`
`INTRODUCTION
`
`This is the second challenge to the claims of U.S. Patent No. 11,253,572
`
`(“the ’572 Patent,” Ex.1001) at this Board. As in the previous challenge by
`
`Apotex, where institution was denied,1 Petitioner argues that the Challenged
`
`Claims are invalid based on Regeneron’s own disclosures of certain information
`
`regarding its clinical trials. But despite Petitioner using that prior challenge as a
`
`roadmap, the present challenge fails for similar reasons.
`
`Like the claims challenged in the previous petition, virtually all the
`
`remaining Challenged Claims2 require not just a particular dosing regimen of
`
`aflibercept, but also require that the patient achieve certain visual acuity results,
`
`which the Board previously referred to as “results limitations.” The Board
`
`previously ruled that these limitations have patentable weight and found that prior
`
`art disclosure of the dosing regimens failed to inherently disclose those results.
`
`Ex.1004, 34. Petitioner employes three general approaches in its attempt to avoid
`
`the Board’s prior decision.
`
`
`1 Apotex Inc. v. Regeneron Pharmaceuticals, Inc., IPR2022-01524, Paper 9
`
`(P.T.A.B. Mar. 10, 2023) (“Apotex Institution Denial”).
`
`2 All but Claims 15, 24, and 25.
`
`
`
`1
`
`Biocon Exhibit 1067 Page 13
`
`

`

`IPR2023-00884
`
`
`
`
`
`First, Petitioner insists that it is arguing obviousness in Grounds IV-VIII, not
`
`anticipation. But the law of inherency is enforced with greater strictness in the
`
`obviousness context. Where the prior art lacks express disclosure of results, a
`
`possibility, or even a probability of the claimed results is insufficient.
`
`Second, in Grounds II-III and V-VIII, Petitioner contends that the prior art
`
`expressly discloses the claimed results limitations. But the references Petitioner
`
`relies on share two fatal features: They are from less than a year before the
`
`conceded priority date, and they report on the results of the Patent Owner
`
`Regeneron’s own clinical trials. Common sense dictates that Regeneron and
`
`Dr. Yancopoulos (the company’s Chief Scientific Officer and the patent’s sole
`
`inventor) completed those trials and perfected the invention before the results were
`
`reported. That means those references are not prior art, both because the invention
`
`was conceived and reduced to practice before the reference was published, and
`
`because the relied-upon disclosures were derived from the inventor himself.
`
`Petitioner’s failure to offer any evidence supporting its assertion that these
`
`references are prior art is fatal to the associated grounds.
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`Third, in Grounds X and XI, Petitioner argues that the results limitations
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`lack patentable weight. But the Board already rejected this argument in the Apotex
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`Institution Denial.
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`2
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`Petitioner’s Ground IX challenges the sole ’572 claim that requires four
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`monthly secondary doses after an initial dose, followed by tertiary doses every
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`eight weeks. The prior art does not teach four monthly secondary doses, and
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`Petitioner does not articulate why a POSA would have modified the prior art to
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`arrive at the recited regimen.
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`Petitioner’s remaining ground, Ground I, relies in part on a reference from
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`2010 that is not prior art, and in part on the disclosure of a Phase II clinical trial.
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`Even though Petitioner concedes that the preamble of the challenged claims
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`requires administering a VEGF antagonist for the purpose of improving a patient’s
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`angiogenic eye disorder, it points to no disclosure of such a purpose in the prior art.
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`Each of these flaws is apparent from the face of the Petition, and therefore,
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`institution should be denied.
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`II. BACKGROUND
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`A. EYLEA®
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`The FDA in 2011 approved aflibercept, under the brand name EYLEA®, for
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`treatment of wet AMD. Ex.2001 ¶ 64. Approval for another angiogenic eye
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`disorder, diabetic macular edema (DME), followed in 2014. Id. ¶ 67. Despite
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`debuting five years after other anti-VEGF agents, EYLEA® is now the anti-VEGF
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`therapy most commonly used for both wet AMD and DME. Id. ¶¶ 64-67, 69. Its
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`popularity is largely due to the fact that it is able to not just halt progression of
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`3
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`disease, but provide for visual acuity gains comparable to other anti-VEGF
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`options—and do so with less frequent dosing. Id. ¶¶ 29, 86-89, 93. Unlike
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`Genentech’s Lucentis, whose label requires monthly administration for wet AMD
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`and DME, EYLEA® can be administered every eight weeks. Id. ¶¶ 40-41. This
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`eight-week dosing follows an initial “primary” dose and a certain number of
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`“secondary” doses, administered monthly: For wet AMD, the label directs two
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`secondary doses, and for DME, it directs four. Ex.2002 §§ 2.2, 2.4.
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`1.
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`Development of Eylea® for AMD
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`Dr. George Yancopoulos, Regeneron’s co-founder, president, and chief
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`scientific officer, came up with the idea to use two secondary doses every four
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`weeks followed by tertiary doses every eight weeks, and he tested the efficacy of
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`this regimen in the Phase III VIEW clinical trials.
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`The VIEW trials followed Regeneron’s Phase I and II trials, called
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`CLEAR-IT-1 and CLEAR-IT-2, respectively. Ex.1009, 3-4. CLEAR-IT-1 and
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`CLEAR-IT-2 used different dosing regimens than the one the EYLEA label
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`recommends. See Ex.2003, 137:22-24.3 For CLEAR-IT-1, each of the 21 subjects
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`received a single injection of 0.05 to 4 mg. Ex.1009, 3. For CLEAR-IT-2,
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`Regeneron tested dose amounts from 0.5 to 4 mg. Ex.1009, 4. In the first
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`3 Citations to Ex.2003 use the transcript’s original page and line numbers.
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`4
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`12 weeks, subjects were randomized to receive injections either monthly or
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`quarterly. Id. Then, all subjects were treated on a PRN (as-needed) basis. Id.
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`Regeneron and Dr. Yancopoulos obtained positive interim results from
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`CLEAR-IT-2 in late March 2007. Ex.2004; Ex.2005; Ex.2006.
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`Around this time, Dr. Yancopoulos came up with the idea to test a dosing
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`regimen of two secondary doses every four weeks followed by doses every eight
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`weeks. See Ex.2003, 137:3-6. Dr. Yancopoulos realized that a dose of
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`Genentech’s anti-VEGF agent, Lucentis, did not last two months—in the two
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`months after an injection, patients would gain vision and then lose vision before
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`the next injection. Ex.2003, 131:5-23; Ex.2007, 47; Ex.1015, 2. Dr. Yancopoulos
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`hoped that aflibercept could last longer and be dosed every two months. Ex.2003
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`131:24-132:5, 137:7-21; Ex.2007, 44. This less-frequent dosing would, in
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`Dr. Yancopoulos’s words, “halve the treatment burden” and “provide a major
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`advance.” Ex.2003 131:24-132:5, 134:11-14, 135:24-136:3, 137:7-21.
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`Dr. Yancopoulos initially decided to pair this eight-week dosing with three
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`preceding monthly doses. Ex.2003 133:17-20; 137:3-6, 137:15-21; see Ex.2008.
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`Regeneron selected 2 mg as the highest dose for the VIEW trials because, as
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`Dr. Yancopoulos recognized, the 4 mg dose provided a limited benefit and could
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`result in additional toxicities during the phase III trial. Ex.2003, 125:22-126:16;
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`135:7-12; Ex.2009, 2. In April 2007, Regeneron selected the arms for the VIEW
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`5
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`trial design, which included the “2q8” arm, in which subjects received 2 mg
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`aflibercept in two secondary doses followed by tertiary doses every eight weeks.
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`Ex.2003, 133:10-25, 136:19-137:2; see Ex.2008.
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`With Dr. Yancopoulos’s guidance, Regeneron then carried out the VIEW
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`trial. Ex.2003, 150:18-21; see also Ex.2003, 1231:10-15, 1231:21-23. Regeneron
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`announced in September 2009 that it had completed enrollment in the VIEW trials,
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`and the trial was completed in September 2010. Ex.1005, 1, Ex.1038, 3. On
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`November 19, 2010, Dr. Yancopoulos received the VIEW results. Ex.2010;
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`Ex.2011, 4-6. Three days later, on November 22, Regeneron published the top-line
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`VIEW results in the November 2010 Press Release. Ex.1007.
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`2.
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`Development of Eylea® for DME
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`After starting the VIEW trial, Regeneron began testing the same 2q8
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`regimen for DME patients in its Phase II DA VINCI trial. Regeneron had
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`completed its Phase I trial, CLEAR-IT DME, in 2007. Ex.1030; Ex.2012. The
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`five subjects in CLEAR-IT-DME each received a single 4 mg injection. Ex.1030,
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`Ex.1009, 3. Regeneron selected five treatment arms for its DA VINCI trial in
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`mid-2008, including a 2q8 arm that matched 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.2014, 2;
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`Ex.2003, 1615:17-18; Ex.2015, 3.
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`The 24-week primary endpoint results in DA VINCI were available within
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`Regeneron by early 2010. Ex.2014, 2; Ex.2016, 6; Ex.2003, 1615:18-19.
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`Dr. Yancopoulos received these results on February 1, 2010. Ex.2017; Ex.2018;
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`Ex.2019, 13-14. On February 18, Regeneron published the top-line 24-week
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`results in a press release. Ex.2020. Regeneron then sought to present these results
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`at the 2010 meeting of the Association for Research in Vision and Ophthalmology
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`(ARVO). It provided an abstract summarizing the 24-week results to Drs. David
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`Brown and James Major who, after making minor edits, submitted it to the 2010
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`ARVO meeting on March 3. Ex.2021; compare Ex.2022 with Ex.1010; Ex.2023.
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`Regeneron completed the DA VINCI trial and then, on December 8, 2010,
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`Dr. Yancopoulos received the one-year results. Ex.2024; Ex.2015. On
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`December 20, Regeneron reported the top-line one-year results in the December
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`2010 Press Release. Ex.1006.
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`B.
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`’572 Patent
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`The ’572 Patent discloses and claims eight-week extended dosing regimens
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`for aflibercept and the successes achieved while using it. The patent is directed to
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`therapeutic treatments for angiogenic eye disorders (including wet AMD and
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`DME) to achieve certain results. Ex.1001, 2:13-16, 38, 42-46, 61-67, 3:38-41,
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`5:30-49. All but three of the remaining Challenged Claims require not only a
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`particular dosing regimen, but also that the patient achieve certain visual acuity
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`results.4
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`The ’572 Patent claims priority on its face to provisional application
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`No. 61/434,836, filed on January 21, 2011, shortly after the one-year results of the
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`VIEW and DA VINCI trials became available to Regeneron. Ex.1001. The
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`provisional application reports both the trial protocol and results for the VIEW and
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`DA VINCI trials. See Ex.2025, ¶¶ 58-60 (VIEW), ¶¶ 61-62 (DA VINCI); Ex.1001
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`at 13:10-27 (VIEW), 14:32-15:12 (DA VINCI).
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`C. Apotex Petition
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`In 2022, Apotex Inc. filed a petition against claims 1-14 and 26-30 of the
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`’572 Patent. Ex.1004, 2. The Board denied institution on March 10, 2023, a
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`month and a half before Samsung filed its petition. Id.
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`In that prior petition, Apotex “assert[ed] that the results limitations merely
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`state the intended results of the otherwise claimed methods of administering
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`aflibercept and, as such, have no patentable weight.” Id. at 15. The Board
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`disagreed. The Board analogized to Los Angeles Biomedical Research Institute at
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`4 Claim 25 differs from the other claims by requiring four secondary doses, which
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`the prior art does not disclose or teach. Claims 15 and 24 require a “method of
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`treatment,” which the Petitioner’s prior art does not disclose.
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`8
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`Harbor-UCLA Medical Center v. Eli Lilly & Co., 849 F.3d 1049 (Fed. Cir. 2017)
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`(“LA Biomed”), where results limitations carried patentable weight. In LA Biomed,
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`the claims “included a limitation in the body of the independent claim to a
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`treatment result of ‘arresting or regressing’ a tissue fibrosis by the administration
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`of the recited dosage.” Ex.1004, 16 (citing LA Biomed., 849 F.3d at 1053-54). In
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`the Apotex Institution Denial, the Board recognized that “because the phrase was
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`drafted as a part of a separate step of the method rather than of the preamble, the
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`‘arresting or regressing’ language demanded efficacy.” Id. at 17 (citing LA
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`Biomed., 849 F.3d at 1060-61). The Board therefore concluded that the results
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`limitations of the Challenged Claims in the ’572 Patent “are limitations and must
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`be given patentable weight for the same reasons arresting or reg