`
`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.: IPR2021-008801
`
`
`U.S. Patent No. 9,669,069 B2
`Filed: December 17, 2015
`Issued: June 6, 2017
`Inventor: George D. Yancopoulos
`
`Title: USE OF A VEGF ANTAGONIST TO TREAT
`ANGIOGENIC EYE DISORDERS
`
`
`
`
`
`PETITIONER’S DEMONSTRATIVES FOR ORAL ARGUMENT
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1 IPR2022-00257 and IPR2022-00301 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
`
`H
`
`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 VEGFR1R2ΔC1(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 aflibercept
`(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, 1577
`
`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.1006, Dixon, 1576
`
`Ex.1020, Heier-2009, 45
`
`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).
` Clear, plain and ordinary meaning
` Supported by and consistent with intrinsic record (including express definitions)
`• Prior art disclosed exact Q8 regimen (VIEW)
`(E.g., Dixon (Ex.1006))
`• PO now tries to rewrite the Claims /
`sow confusion over “VEGF Trap-Eye”
`
`Ex.1001, Fig. 1 (modified)
`
`Grounds 1-5 (Anticipation)
`
`Ground 6 (Obviousness)
`
`1. Dixon
`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
`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)
`o Extrinsic evidence
`o Clear intrinsic record
`o Contradicts intrinsic record
`o Preserves the intended scope and
`patent’s notice function
`o Eliminates notice function
`o Applies to all embodiments
`o Excludes embodiments
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`• “treating” requires a “high level of efficacy”
`(Paper 73, 3)
`
`33
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsic Evidence – The 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.”))
`
`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):
`Intrinsic Evidence – The 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):
`Intrinsic Evidence – The 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):
`Intrinsic Evidence – The 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
`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
`
`37
`
`(Paper 61, 7-12)
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsic Evidence – The Specification
`Intrinsic evidence expressly defines “therapeutically effective
`amount” as doses resulting in all levels 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, 6:48-58
`Compare with “exhibits a loss of 15 or fewer letters
`on the [ETDRS]” (Ex.1001, ’338 patent, 7:26-29)
`
`(Paper 61, 7-12)
`
`EYLEA = 2.0 mg
`(Ex.1091, Eylea PI)
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`38
`
`
`
`’338 Patent: Claim Construction
`“method for treating an angiogenic eye disorder in a patient”
`Challenged Claim 1 (’338 Patent):
`Intrinsic Evidence – The 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
`
`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):
`Intrinsic Evidence – The 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
`(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):
`Intrinsic Evidence – The Prosecution 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; 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):
`Intrinsic Evidence – The Prosecution 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”
`Patent Owner’s Proposal:
`
`Requiring a “high level of efficacy” in the form of “visual acuity
`gains” excludes embodiments
`
`Ex.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)
`
`“treat[ing] requires a high level of efficacy”
`
`“visual acuity gains became the new standard-
`of-care in treating wAMD”
`
`(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”
`Patent Owner’s Proposal:
`
`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”
`
`“visual acuity gains became the new standard-
`of-care in treating wAMD”
`
`(Paper 73, 3-4; Paper 40, 12-13; see also Paper 61,
`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):
`Intrinsic Evidence – 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)”
`Patent Owner’s Proposal:
`
`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)”
`Patent Owner’s Proposal:
`
`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
`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
`
`
`
`’338 Patent: Claim Construction
`“initial dose,” “secondary dose(s)” & “tertiary dose(s)”
`Patent Owner’s Proposal:
`
`PO’s current proposal significantly differs from, and is
`inconsistent with, its prior construction for the same term
`
`[PGR2021-00035 (U.S. 10,828,345)] PO: “tertiary dose(s)”
`means “dose(s) that maintain(s) a therapeutic effect throughout
`the course of treatment” Ex.1141, 23-25
`(Paper 1, 13-14 & n.4; Paper 61, 16-17)
`
`Specification expressly defines “therapeutically effective
`amount” as encompassing doses that “lessen[] or delay[]” the
`progression of an angiogenic eye disorder, i.e., not limited to
`only “a high level of efficacy.” See Ex.1001, ’338 patent, 6:48-58
`
`Ex.1138, Do Dep. Ex.4
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`48
`
`
`
`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)
`“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.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
`immediately preceding dose; and
`
`… 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)
`
`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
`WW.RMMSLEGAL.COM
`
`
`
`’069 Patent
`
`Ex.1001, ’069 Patent, 2:30-38
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`54
`
`
`
`Dixon
`
`Ex.1006, Dixon, 1575
`
`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 Demonstratives for Oral Argument was served on August 5, 2022, via
`
`electronic mail by agreement of the parties, to the following counsel for record of
`
`Patent Owners:
`
`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
`
`
`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
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`/Paul J. Molino/
` Paul J. Molino (Reg. No. 45,350)
`
`
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
