`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`MYLAN PHARMACEUTICALS INC., CELLTRION, INC., and
`APOTEX, INC.,
`Petitioners,
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`
`Inter Partes Review No.: IPR2021-008811
`
`
`U.S. Patent No. 9,254,338 B2
`Filed: July 12, 2013
`Issued: February 9, 2016
`Inventor: George D. Yancopoulos
`
`Title: USE OF A VEGF ANTAGONIST TO TREAT
`ANGIOGENIC EYE DISORDERS
`
`
`
`
`
`PETITIONER’S CORRECTED DEMONSTRATIVES FOR ORAL
`ARGUMENT
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1 IPR2022-00258 and IPR2022-00298 have been joined with this proceeding.
`
`
`
`Mylan Pharmaceuticals Inc. v.
`Regeneron Pharmaceuticals, Inc.
`IPR2021-00880 & IPR2021-00881
`Petitioner, Mylan Pharmaceuticals Inc.
`--Oral Argument--
`
`August 10, 2022
`
`
`
`’069 Patent: Anticipation Grounds 1-3
`• The dosing regimen disclosures of Dixon, Heier-2009, and Regeneron
`April 2009 Press Release are undisputed.
`E.g., Dixon (Ground 2) discloses the VEGF Trap-Eye CLEAR-IT-2 trial: PRN dosing after 4
`monthly loading doses (i.e., an initial dose and one or more secondary doses)
`• Heier-2009 (Ground 1)
`discloses the same trial and
`regimen (Ex.1020)
`(IPR2021-00880, Paper 1, 32-36, 45-50)
`
`•
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`2
`
`Ex.1006, Dixon, 1576
`
`
`
`’069 Patent: Anticipation Grounds 1-3
`• The dosing regimen disclosures of Dixon, Heier-
`2009, and Regeneron April 2009 Press Release
`are undisputed.
`The Press Release discloses the VEGF Trap-Eye Phase 3 CRVO
`trials - PRN dosing after six monthly loading doses (i.e., an
`initial dose and one or more secondary doses)
`(IPR2021-00880, Paper 1, 45-53)
`
`•
`
`Ex.1028, Regeneron (30-April-2009)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`3
`
`
`
`•
`
`’069 Patent: Anticipation Grounds 1-3
`• Thus, Petitioner’s asserted
`references cover each and
`every limitation of the claims
`It is undisputed that the references
`disclose the dosing regimen steps
`and the molecule, VEGF Trap-Eye,
`also known as aflibercept
`The sole dispute over Petitioner’s
`anticipation grounds is over the
`sequence element
`(IPR2021-00880, Paper 68, 25-36)
`
`•
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`4
`
`Ex.1001, ’069 patent, claim 1
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• Claim 1 of each patent sets forth the
`sequence of VEGF Trap-Eye/aflibercept
`(IPR2021-00880, Paper 1, 45-50; IPR2021-00881, Paper 1, 39-44)
`
`Ex.1001, ’338 patent, claim 1
`
`Ex.1001, ’069 patent, claim 1
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`5
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• No confusion among
`POSAs
`• Dixon discloses the use of
`VEGF Trap-Eye/aflibercept in
`AMD
`
`(IPR2021-00880, Paper 1, 26-34, 54-58; Paper 56, 10-15)
`(IPR2021-00881, Paper 1, 23, 39-44; Paper 61, 23-27)
`
`Ex.1006, Dixon, 1573
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`6
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• No confusion among POSAs
`• Adis discloses the use of VEGF Trap-Eye/aflibercept in AMD
`
`(IPR2021-00880, Paper 1, 26-34, 54-58; Paper 56, 10-15)
`(IPR2021-00881, Paper 1, 23, 39-44; Paper 61, 23-28)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Ex.1007, Adis, 261, 264
`
`7
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• No confusion among POSAs
`The aflibercept sequence was publicly available
`(IPR2021-00880, Paper 1, 26-29, 38-39; Paper 56, 7-9, 13-15)
`(IPR2021-00881, Paper 1, 24-25, 36-37; Paper 61, 22-28)
`
`•
`
`Ex.1107, WHO 2006 Drug Info, 118-119
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`8
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• No confusion among POSAs
`The VEGF Trap-Eye/aflibercept sequence was available to interested POSAs
`(IPR2021-00880, Paper 1, 26-29, 38-39;
`Paper 56, 7-9, 13-15)
`(IPR2021-00881, Paper 1, 24-25, 36-37;
`Paper 61, 22-28)
`
`•
`
`Ex.1004, Holash, 11397
`
`Ex.1010, ’758 Patent, 10:15-17
`
`
`
`HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH
`
`Ex.1008, ’173 Patent, 1:48-52
`
`Multiple VEGF Trap-Eye and aflibercept references refer back to Holash:
`• Ex.2080, Heier (“VEGF Trap-Eye includes specific extracellular components of VEGF receptors 1
`and 2 fused to the constant region (Fc) of IgG1,” and citing to, and presenting data from, Holash)
`• See also, e.g., Ex.1119 (referencing aflibercept and citing Holash); Ex.1120 (same); Ex.1123
`(discussing VEGF Trap-Eye and citing Holash); Ex.1115, Gerritsen Reply Decl., ¶¶ 36-56
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`9
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• No confusion among POSAs
`Ex.1122: ’069/’338 claimed sequence =
`prior art 2006 WHO Drug Info aflibercept
`sequence (Ex.1107) = prior art ’758/’959
`Fig. 24 sequence of VEGFR1R2(cid:564)C1(a) (SEQ
`ID NO: 16) (Ex.1010)
`
`•
`
`•
`
`See also, e.g., Ex.1117 (aligning the ’338
`claimed sequence, the WHO aflibercept
`sequence, and the ’173 patent, SEQ ID NO:2
`sequence)
`(IPR2021-00880, Paper 56, 13-15)
`(IPR2021-00881, Paper 61, 27-28)
`
`Ex.1122, Amino Acid Alignment (see also,
`e.g., Ex.1024 (Nucleic Acid Alignment))
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`10
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• PO’s counter-arguments lack merit
`• Dixon discloses that VEGF Trap-Eye and
`aflibercept have the “same molecular
`structure.” Ex.1006, 1575
`• Any other trap species would have a different
`
`molecular structure from afliberceptp
`(IPR2021-00880, Paper 56, 10-16)
`(IPR2021-00881, Paper 61, 23-27)
`
`Ex.1108, Klibanov Tr., 32-35; 184:1-189:10
`Ex.1103, Klibanov Dep. Ex. 3, ¶¶ 76, 82-83
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`11
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• PO’s counter-arguments lack merit
`VEGF Trap-Eye not a genus
`•
`• Dixon and Adis refer to the agent in the singular, and disclose it in
`Phase 2 and Phase 3 clinical trials
`Regeneron’s public disclosures make clear the ophtho and onco
`products contained the same active ingredient (aflibercept)
`(IPR2021-00880, Paper 56, 13-15; IPR2021-00881, Paper 61, 26-27)
`
`•
`
`Ex.1021, 2009 10-Q, 18-19
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`12
`
`
`
`’338 and ’069 Patents: The claimed molecule
`• PO’s counter-arguments lack merit
`Regeneron’s public disclosures make clear the ophtho and onco
`products contained the same active ingredient (aflibercept)
`
`•
`
`•
`
`Ex.1113, Rudge 2008 at 417-418:
`“promising results…supported the
`introduction of VEGF Trap into the
`clinic for treatment of both wet
`AMD and diabetic macular
`edema, using a version of VEGF
`Trap specifically formulated for
`intra-ocular administration,
`termed VEGF Trap-Eye.”
`(IPR2021-00880, Paper 56, 13-15)
`(IPR2021-00881, Paper 61, 26 n.13, 26-28)
`
`Ex.1113, Rudge 2008, 415
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`13
`
`
`
`IPR2021-00880 – Ground 4
`• PO Should Be Held To Its Prosecution Representations
`“In accordance with a dosage regimen as claimed in independent claim 1”
`(IPR2021-00880, Paper 56, 18-20)
`
`•
`
`Ex.1017, ’069 PH, 136-137
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`14
`
`
`
`IPR2021-00880 – Ground 4
`• Dixon Anticipates
`• Dixon discloses VIEW’s second year of PRN dosing
`(IPR2021-00880, Paper 56, 20-21)
`
`Ex.1006, Dixon, 1576
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`15
`
`
`
`IPR2021-00880 – Ground 4
`• Dixon Renders Obvious
`3 monthly loading doses + PRN maintenance
`(IPR2021-00880, Paper 56, 21-24)
`
`•
`
`Ex.1006, Dixon, 1576
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`16
`
`
`
`IPR2021-00880 – Ground 4
`• Dixon Renders Obvious
`• Dixon sets forth motivation . . .
`(IPR2021-00880, Paper 56, 21-24, 25-31)
`
`
`
`Ex.1006, Dixon, 1574, 1577E
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`17
`
`
`
`IPR2021-00880 – Ground 4
`• Dixon Renders
`Obvious
`• Dixon provides
`motivation and a
`reasonable expectation
`of success . . .
`(IPR2021-00880, Paper 56, 21-24)
`
`Ex.1006, Dixon, 1576
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`18
`
`
`
`IPR2021-00880 – Ground 4
`• PO counter-arguments lack merit
`• Abundant evidence of motivation to minimize
`number of injections
`(IPR2021-00880, Paper 1, 58-59; Ex.1002, Dr.
`Albini Decl., ¶¶ 59-60, 168-171)
`• Demonstrated ability to minimize injections using a
`PRN regimen
`•
`PRN Phase 2 = 5.6 injections in first year
`•
`Every-8-week dosing = 8 injections in first year
`• Monthly = 12 injections in first year
`(IPR2021-00880, Paper 1, 60)
`(IPR2021-00880, Paper 56, 21-24, 25-31)
`
`Ex.1002, Dr. Albini Decl., ¶ 59
`
`Ex.1002, Dr. Albini Decl., ¶ 171
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`19
`
`
`
`IPR2021-00880 – Ground 4
`• PO counter-arguments lack merit
`PRN dosing not burdensome
`•
`• Nothing in claims or specification about PRN requiring monthly visits
`PO disregards PRN/as-needed regimens that did not involve monthly visits (Ex.2103,
`•
`2-3; Ex.1049, 24)
`(IPR2021-00880, Paper 56, 21-24, 31-36)
`
`Ex.2103, Retinal Physician, 2
`
`Ex.1110, Brown Tr., 149:15-17
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`20
`
`
`
`IPR2021-00880 – Ground 4
`• PO counter-arguments lack merit
`’069 claims directed to the prevailing trend for treating AMD (Ex.2259, 17; Ex.2103, 2-3)
`•
`• Dr. Albini testified that minimizing injections was the primary focus
`(IPR2021-00880, Paper 56, 18-35)
`
`Ex.1114, Dr. Albini Reply Decl., ¶ 28
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`21
`
`
`
`IPR2021-00880 – Ground 4
`• PO counter-arguments lack merit
`Regeneron implemented PRN dosing in at least six clinical trials prior to 2010
`(IPR2021-00880, Paper 56, 20-24)
`
`•
`
`Trial
`CLEAR-IT-2 (Phase 2)
`VIEW1 & VIEW2 (Phase 3)
`DME (Phase 2)
`COPERNICUS (Phase 3)
`GALILEO (Phase 3)
`
`Disorder
`AMD
`AMD
`DME
`CRVO
`CRVO
`
`Evidence
`Ex.1020; Ex.1006; Ex.1055
`Ex.1006
`Ex.1068
`Ex.1028
`Ex.1028
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`22
`
`
`
`IPR2021-00880 – Ground 5
`• Heier-2009 (PRN dosing) + Dixon/Mitchell (3 monthly loading doses)
`render obvious
`• Heier-2009 = successful PRN dosing
`• Heier-2009 showed significant
`increases in visual acuity with only
`7.5 doses over 18 months (4 loading
`doses + 3.5 PRN doses over next 15
`months)
`(IPR2021-00880, Paper 56, 25-31)
`
`Ex.1020, Heier-2009, 45
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`23
`
`
`
`IPR2021-00880 – Ground 5
`• Heier-2009 (PRN dosing) +
`Dixon/Mitchell (3 monthly
`loading doses) render obvious
`• Dixon = 3 monthly loading doses of
`aflibercept in AMD
`(IPR2021-00880, Paper 56, 25-31)
`
`Ex.1006, Dixon, 1576
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`24
`
`
`
`IPR2021-00880 – Ground 5
`• Heier-2009 (PRN dosing) +
`Dixon/Mitchell (3 monthly
`loading doses) render obvious
`• Mitchell = 3 monthly loading doses
`of anti-VEGF therapy in AMD
`(IPR2021-00880, Paper 56, 25-31)
`
`Ex.1030, Mitchell, 5, 6
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`25
`
`
`
`IPR2021-00880 – Ground 5
`• Heier-2009 (PRN dosing) + Dixon/Mitchell (3 monthly
`loading doses) render obvious
`• Motivation: Reducing injection frequency
`(IPR2021-00880, Paper 56, 25-36)
`
`Ex.1006, Dixon, 1576
`
`Ex.1020, Heier-2009, 45
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`26
`
`
`
`IPR2021-00880 – Ground 5
`• Heier-2009 (PRN dosing) + Dixon/Mitchell (3 monthly
`loading doses) render obvious
`Reasonable expectation of success: improvements in visual acuity
`and retinal thickness in CLEAR-IT-2
`(IPR2021-00880, Paper 1, 60-69, Paper 56,
`27, 31-36); Ex.1002, Dr. Albini Decl., ¶¶ 95-
`96, n.15
`
`•
`
`
`
`Ex.1006, Dixon, 1576E 1
`
`
`
`Ex.1020, Heier-2009, 45 E 1020 H i
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`27
`
`
`
`IPR2021-00880 – Ground 5
`• PO counter-arguments lack merit
`• Motivation to reduce injections not
`limited to “chronic dosing”
`• Mitchell expressly suggested fewer
`loading doses
`(IPR2021-00880, Paper 56, 25-28, 34-35)
`
`Ex.1030, Mitchell, 2, 4
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`28
`
`
`
`•
`
`IPR2021-00880 – Ground 5
`• PO arguments lack merit
`CLEAR-IT-2 data would not
`discourage 3 monthly loading
`doses
`• Dixon disclosed the
`implementation of 3 loading
`doses for Phase 3 VIEW trials, i.e.,
`dropping from 4 loading doses
`(Phase 2) to three loading doses
`(Phase 3)
`(IPR2021-00880, Paper 56, 20-26, 34-36)
`
`Ex.1006, Dixon, 1576
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`29
`
`
`
`•
`
`IPR2021-00880 – Ground 5
`• PO arguments lack merit
`CLEAR-IT-2 data would not
`discourage 3 monthly loading
`doses
`• Dr. Brown argues that the typical
`practice was to treat with loading
`doses until the retina was dry
`(Ex.2050, ¶¶ 141-142)
`• No significant change in retinal
`thickness after the first couple
`loading doses (Ex.1114, Albini
`Reply, ¶ 33)
`(IPR2021-00880, Paper 56, 31-36)
`
`Ex.1055, Retina Society, 18 (emphasis added)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`30
`
`
`
`IPR2021-00881 (U.S. Patent No. 9,254,338)
`
`• Challenged Claims: 1, 3-11, 13-14, 16-24, and 26
`• Claims broadly directed to administering VEGF Trap-Eye under a specific temporal
`sequences of doses (i.e., “Q8” dosing).
`(cid:190) Clear, plain and ordinary meaning
`(cid:190) Supported by and consistent with intrinsic record (including express definitions)
`• Prior art disclosed exact Q8 regimen (VIEW)
`(VIEW)
`
`(E.g., Dixon (Ex.1006))(E.g., Dixon (Ex.1006))
`
`
`
`PO now tries to rewrite the Claims / PO now tries to rewrite the Claimaims / msaim
`
`
`sow confusion over “VEGF Trapapap-pp--Eye”
`
`•
`
`Ex.1001, Fig. 1 (modified)
`
`Grounds 1-5 (Anticipation)
`
`Ground 6 (Obviousness)
`
`
`1. Dixonon
`2. Adis
`3. REG (8-May-2008)
`6. Dixon (alone or combined with the ’758 patent or Dix)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`4 NCT 795
`4. NCT-795
`5. NCT-377
`
`31
`
`
`
`Person of Ordinary Skill in the Art (“POSA”)
`
`Patent Owner
`• POR and Dr. Do: Disagree with Petitioner’s
`definition; POSA must be a licensed physician
`(ophthalmologist).
`(Ex.2051, Do Decl., ¶28)
`• Sur-reply: “[T]he Board need not make specific
`findings as to the level of the POSA.”
`(Paper 73, 2)
`
`• Board: “Petitioner’s definition of [a POSA] is
`reasonable and consistent with the [challenged]
`patent and prior art of record.”
`(Paper 21, 15)
`• Petitioner Reply: PO experts applied different,
`incompatible POSA perspectives; Inventor and
`Dr. Klibanov not a POSA under PO’s definition.
`(Paper 61, 4-6)
`• “The level of skill in the art is a factual determination that provides a
`primary guarantee of objectivity in an obviousness analysis.”
`(Paper 21, 15 (citing Al-Site Corp. v. VSI Int’l, Inc., 174 F.3d 1308, 1323 (Fed. Cir. 1999))).
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`32
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Patent Owner
`• “where a ‘method for treating’ is limiting, the
`claims require efficacy”
`(Paper 73, 2)
`
`• Board: “[T]he preambles of the independent
`claims do not require the recited method steps
`to provide an effective treatment.” (Paper 21, 21)
`• Petitioner: If limiting: “administering a
`therapeutic to a patient, without a specific
`degree of efficacy required” (Paper 1, 20-22)
`• Petitioner: Claims encompass all levels of
`efficacy, not just a “high” one (Paper 61, 9)
`
`• “treating” requires a “high level of efficacy”
`(Paper 73, 3)
`
`o Clear intrinsic record
`o Preserves the intended scope and
`patent’s notice function
`o Applies to all embodiments
`
`o Extrinsic evidence
`o Contradicts intrinsic record
`o Eliminates notice function
`o Excludes embodiments
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`33
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Claims
`
`Petitioner: If limiting: “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`Ex.1001, ’338 patent, claim 1
`
`Plain language of the Claims do not set forth any efficacy
`requirement. (Paper 1, 20-22; see also Paper 61, 7-8 (quoting Kaneka)
`(“Claim construction begins with the language of the claims.”))
`( Claim construction begins with the language of the claims. ))
`
`Ex.1001, ’338 patent, 23:2-24:53 (claims)
`
`Board: “Patent Owner does not direct us to any other portion
`of the claims … that supports finding that the claimed method
`for treating … requires such treatment method to have any
`particular level of effectiveness.” (Paper 21, 20)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`34
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Specification
`Intrinsic record describes the method as sequentially
`administered doses (no mention of efficacy)
`
`Petitioner: If limiting: “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`Ex.1001, ’338 patent, claim 1
`
`Ex.1001, ’338 patent, 2:14-15, 54-55, Fig.1, 3:19-26 (Paper 61, 2, 9-10)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`35
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Specification
`Intrinsic evidence expressly encompasses
`all levels of efficacy, not just a “high” one
`
`Petitioner: If limiting: “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`Ex.1001, ’338 patent, claim 1
`
`Ex.1001, ’338 patent, 1:44-48, 7:15-21
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`(Paper 61, 7-12)
`
`36
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Specification
`Intrinsic evidence expressly encompasses
`all levels of efficacy, not just a “high” one
`
`Petitioner: If limiting: “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`Ex.1001, ’338 patent, claim 1
`
`
`
`
`
`
`
`Ex.1001, ’338 patent, 2:3-10 patent, 2patent 2:t t 2:3:33-10 1010
`
`
`
`
`
`
`Board: “Without more, we do not find the
`disclosure that such effects ‘can be achieved’
`demonstrates adequately that the claims require
`any particular level of efficacy.” (Paper 21, 21)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`
`
`(Paper 61, 7-12)(Paper 61, 7(Paper 61, 7-12)12)(P 61 7 12
`
`37
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Specification
`Intrinsic evidence expressly defines “therapeutically effective
`amount” as doses resulting in all levels of efficacy
`f
`ff
`y
`g
`
`Petitioner: If limiting, “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`Ex.1001, ’338 patent, claim 1
`
`Ex.1001, ’338 patent, 6:48-58
`
`(Paper 61, 7-12)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`38
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Specification
`“Efficacy” is expressly defined “[i]n the context of methods for
`treating” covered by the Challenged Claims (e.g., claim 6)
`
`Petitioner: If limiting, “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`
`
`Ex.1001, ’338 patent, 7:24-28 001, ’338 patent, 7:24-28
`
`Ex.1001, ’338 patent, claim 1
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`(Paper 61, 2, 9-10)
`
`39
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Specification
`Background “methods for treating” also make
`no mention of efficacy
`
`Petitioner: If limiting, “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`
`
`Ex.1001, ’338 patent, 1:53-59 Ex.1001, ’338 patent, 1:53-59 E 1001 ’338 t t 1 53 59
`
`
`
`(Paper 61, 9-10, 13; Ex.1114, Albini, ¶ 23)((Paper 61, 9-10, 13; Ex.1114, Albini, ¶ 23)
`
`Ex.1001, ’338 patent, claim 1
`
`Only reference to a “high level of efficacy.”
`Compare with Continental Circuits LLC v. Intel Corp., 915 F.3d 788, 798-99 (Fed. Cir. 2019)
`(absent clear disavowal, a preferred embodiment does not limit claim construction).
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`40
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Prosecutionn History
`PO emphasized treatment protocols and
`g
`q
`y,
`
`dosing frequency, not a “high level of efficacy” g y
`
`
`
`Petitioner: If limiting, “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`Ex.1001, ’338 patent, claim 1
`
`Ex.1017, ’338 PH, 288-90 (Paper 1, 9-10; see also Paper 61, 9-10)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`41
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Thee Prosecutionn History
`PO emphasized treatment protocols and
`dosing frequency, not a “high level of efficacy”
`
`Petitioner: If limiting, “administering a
`therapeutic to a patient, without a
`specific degree of efficacy required”
`(Paper 1, 20-22; Paper 61, 7)
`
`Ex.1001, ’338 patent, claim 1
`
`Ex.1017 , ’338 PH, 288-90 (Paper 1, 9-10)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`42
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Patentt Owner’s’s Proposalal:
`
`Requiring a “high level of efficacy” in the form of “visual acuity
`gains” excludes embodiments
`
`
`
`Ex.1001, ’338 patent, 7:29-32Ex.1001, ’338 patent, 7:29-32
`
`•
`
`“[Courts] normally do not interpret claim terms in a way that excludes
`embodiments….” Oatey Co. v. IPS Corp., 514 F.3d 1271, 1276 (Fed. Cir.
`2008)
`• Absent clear disavowal, a preferred embodiment does not limit claim
`construction. Continental Circuits LLC v. Intel Corp., 915 F.3d 788, 798-99
`(Fed. Cir. 2019)
`
`
`
`Ex.1138, Do Dep. Ex.4 (Paper 61, 7-8)E
`
`
`
`“treat[ing] requires a high level of efficacy”“t
`
`“visual acuity gains became the new standard-
`“v
`of-care in treating wAMD”
`f
`
`(Paper 73, 3-4; Paper 40, 12-13; see also Paper 61,
`13-14)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`43
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Patentt Owner’s’s Proposalal:
`
`Requiring a “high level of efficacy” in the form of “visual acuity
`gains” excludes embodiments
`
`Ex.1138, Do Dep. Ex.4 (Paper 61, 7-8)
`
`
`
`“treat[ing] requires a high level of efficacy”“treat
`
`“visua
`“visual acuity gains became the new standard-
`of-care in treating wAMD”
`of-car
`
`
`(Paper 73, 3-4; Paper 40, 12-13; see also Paper 61, (Paper
`13-14)
`13-14
`
`Dr. Brown (applying “high level of efficacy” construction):
`Example 4 data does not “allow[] me to determine whether it’s a
`method of treatment.” Ex.1110, Brown Tr., 22:17-25:7 (Paper 61, 10)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`44
`
`
`
`’338 Patent: Claim Construction
`“initial dose,” “secondary dose(s)” & “tertiary dose(s)”
`Challenged Claim 1 (’338 Patent):
`Intrinsicc Evidencee ––– Lexicography
`
`Board: “[W]e find that the
`Specification expressly defines the
`terms ‘initial dose,’ ‘secondary
`doses,’ and ‘tertiary doses.’”
`(Paper 21, 22-23)
`
`Ex.1001, ’338 patent, Claim 1
`
`Ex.1001, ’338 patent, 3:31-45
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`45
`
`
`
`’338 Patent: Claim Construction
`“initial dose,” “secondary dose(s)” & “tertiary dose(s)”
`Patentt Owner’s’s Proposalal:
`
`NEW ARGUMENT. PO (Sur-reply): “[I]f the Board chooses to
`construe these terms, PO’s arguments regarding ‘tertiary dose’
`apply with equal force to the ‘initial dose’ and ‘secondary dose’
`terms.”
`(Paper 73, 12; compare with Paper 40, 7 (“‘initial dose’ and
`‘secondary doses’ need not be construed”))
`
`Board: “[W]e do not find that the Specification requires the
`‘tertiary doses’ to maintain any efficacy gain achieved after the
`initial and secondary doses, or that the term ‘connotes a
`specific level of efficacy’” (Paper 21, 22-23)
`
`Ex.1138, Do Dep. Ex.4
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`46
`
`
`
`’338 Patent: Claim Construction
`“initial dose,” “secondary dose(s)” & “tertiary dose(s)”
`Patentt Owner’s’s Proposalal:
`
`PO does even not attempt to construe “tertiary dose(s)”
`separate from its arguments for “method for treating”
`(See Paper 40, 23-24 (incorporating by reference PO’s arguments
`regarding the “method for treating” preamble requiring a high level of
`efficacy); Paper 73, 12-13 (same))
`
`
`PO offers only extrinsic evidence which contradicts the PO offers only extrinsic evidence which contradicts the
`
`intrinsic record on “tertiary dose(s)”ecord
`intrinsic record on “tertiary dose(s)”
`
`Board: “[PO] has not directed us to any portion of the
`Specification that teaches differently or adds any efficacy
`requirement to that definition [of ‘tertiary doses’].”
`Ex.1138, Do Dep. Ex.4
`(Paper 21, 23)
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`47
`
`
`
`Grounds 1-2 (Anticipation)
`Dixon & Adis
`• VIEW Q8 dosing regimen (with 3 loading doses) expressly disclosed
`
`Ex.1006, Dixon, 1576, 1579
`
`Ex.1007, Adis, 263
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`(Paper 1, 27-30, 39-49)
`
`49
`
`
`
`Grounds 3-5 (Anticipation)
`REG (8-May-2008), NCT-795 (VIEW 1) & NCT-377 (VIEW 2)
`• VIEW Q8 dosing regimen (with 3 loading doses) expressly disclosed
`
`(Paper 1, 31-36, 49-61)er 1, 31-36, 49-61)
`“In the first year, the VIEW2 . . .
`study will evaluate the safety and
`efficacy of VEGF Trap-Eye at . . .
`2.0 mg at an 8-week dosing
`interval, including one additional
`2.0 mg dose at week four.”
`(Ex.1013, REG (8-May-2008), 1-2)
`Ex.1013, REG (8-May-2008), 1-2)
`
`Ex.1014,
`NCT-795
`
`“2.0 mg VEGF Trap-Eye
`administered every 8 weeks
`(including one additional 2.0 mg
`dose at week 4) during the first
`year.” (Ex.1014, NCT-795, 8;
`Ex.1015, NCT-377, 6)
`
`Ex.1015, NCT-377
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`50
`
`Ex.1013, REG (8-May-2008)
`
`
`
`Ground 6 (Obviousness)
`Dixon (alone or combined with the ’758 patent or Dix)
`• VIEW Q8 dosing regimen (with 3 loading doses) expressly disclosed
`Claim 1 (’338): A method for treating an angiogenic eye disorder in a patient
`
`… administering to the patient a single initial dose of a VEGF antagonist,
`followed by one or more secondary doses of the VEGF antagonist, followed
`by one or more tertiary doses of the VEGF antagonist
`
`… wherein each secondary dose is administered 2 to 4 weeks after the … wherein each secondary dose is administered 2 to 4 weeks after the
`immediately preceding dose; and
`
`immediately preceding dose; andimmediately preced
`
`… wherein each tertiary dose is administered at least 8 weeks after the
`immediately preceding dose…
`
`Ex.1006, Dixon, 1575-76
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`(Paper 1, 36-37, 62-66)
`
`51
`
`Ex.1010, ’758 Patent, 10:15-17
`
`
`
`Ground 6 (Obviousness)
`Dixon (alone or combined with the ’758 patent or Dix)
`• VIEW Q8 dosing regimen (with 3 loading doses) expressly disclosed
`Reasonable Expectation of Success: Dixon discloses positive
`Phase 2 (“CLEAR-IT-2”) data which launched the VIEW trial.
`Ex.1006, Dixon, 1576 (after 52 weeks, Phase 2 patients
`required (on average) only 1.6 additional injections after four
`monthly loading doses) (Paper 1, 64-65; Paper 61, 32-33)
`y
`g
`) ( p
`p
`)
`
`Ex.1006, Dixon, 1576
`
`Motivation to Combine with the
`’758 patent or Dix: Dixon expressly
`discloses dosing VEGF Trap-Eye
`(Paper 1, 63-64)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`52
`
`
`
`
`
`W W W . R M M S L E G A L . C O M
`
`WWW.RMMSLEGAL.COM
`
`
`
`
`
`’069 Patent
`
`Ex.1001, ’069 Patent, 2:30-38
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`54
`
`
`
`Dixon
`
`
`
`Ex.1006, Dixon, 1575E
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`55
`
`
`
`Dixon
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`56
`
`Ex.1006, Dixon, 1576
`
`
`
`Adis
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`57
`
`Ex.1007, Adis, 261
`
`
`
`’758 PTE Application
`
`Ex.1024, ’758 PTE, 2 (Paper 61, 22)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`58
`
`
`
`’758 PTE Application
`
`Ex.1024, ’758 PTE, 6-7 (Paper 1, 24-25)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`59
`
`
`
`’959 PTE Application
`
`Ex.1102, ’959 PTE, 2 (Paper 61, 30, 36)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`60
`
`
`
`’959 PTE Application
`
`Ex.1102, ’959 PTE, 5 (Paper 61, 30, 36)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`61
`
`
`
`’959 PTE Application
`
`Ex.1102, ’959 PTE, 5 (Paper 61, 30, 36)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`62
`
`
`
`’959 PTE Application
`
`Ex.1102, ’959 PTE, 5-6
`(Paper 61, 30, 36)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`63
`
`
`
`’959 PTE Application
`
`Ex.1102, ’959 PTE, 6-7 (Paper 61, 30, 36)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`64
`
`
`
`
`
`CERTIFICATE OF SERVICE
`
`The undersigned hereby certifies that a true and correct copy of the foregoing
`
`Petitioner’s Corrected Demonstratives for Oral Argument was served on August 9,
`
`2022, via electronic mail by agreement of the parties, to the following counsel for
`
`record of Patent Owners:
`
`Deborah E. Fishman (Reg. No. 48,621)
`David A. Caine (Reg. No. 52,683)
`Arnold & Porter Kaye Scholer LLP
`3000 El Camino Real
`Five Palo Alto Square, Suite 500
`Palo Alto, California 94306-3807
`Telephone: 650.319.4519
`Telephone: 650.319.4710
`Facsimile: 650.319.4573
`Deborah.Fishman@arnoldporter.com
`David.Caine@arnoldporter.com
`RegeneronEyleaIPRs@arnoldporter.com
`
`Daniel Reisner
`Matthew M. Wilk
`Arnold & Porter Kaye Scholer LLP
`250 West 55th Street
`New York, New York 10019-9710
`Telephone: 212.836.8000
`Fax: 212.836.8689
`Daniel.Reisner@arnoldporter.com
`Matthew.Wilk@arnoldporter.com
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Alice S. Ho (Lim. Rec. No. L1162)
`Victoria Reines
`Jeremy Cobb
`Arnold & Porter Kaye Scholer LLP
`601 Massachusetts Ave., N.W.
`Washington D.C. 20001
`Tel: 202.942.5000
`Fax: 202.942.5999
`Alice.Ho@arnoldporter.com
`Victoria.Reines@arnoldporter.com
`Jeremy.Cobb@arnoldporter.com
`
`
`
`/Paul J. Molino/
` Paul J. Molino (Reg. No. 45,350)
`
`