Trials@uspto.gov
`571-272-7822
`
`Paper 94
`Date: November 9, 2022
`
`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.
`
`IPR2021-008811
`Patent 9,254,338 B2
`
`Before ERICA A. FRANKLIN, JOHN G. NEW, and
`SUSAN L. C. MITCHELL, Administrative Patent Judges.
`FRANKLIN, Administrative Patent Judge.
`
`JUDGMENT
`Final Written Decision
`Determining All Challenged Claims Unpatentable
`Denying in part and Dismissing in part Petitioners’ Motion to Exclude
`Denying in part and Dismissing in part Denying Patent Owner’s
`Motion to Exclude
`35 U.S.C. § 318(a)
`
`1 IPR2022-00258 and IPR2022-00298 have been joined with this
`proceeding. See Papers 35 and 36.
`
`
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`IPR2021-00881
`Patent 9,254,338 B2
`
`INTRODUCTION
`I.
`This is a Final Written Decision in an inter partes review of claims 1,
`3–11, 13, 14, 16–24 and 26 (“the challenged claims”) of U.S. Patent
`No. 9,254,338 B2 (Ex. 1001, “the ’338 patent”). We have jurisdiction under
`35 U.S.C. § 6, and enter this Decision pursuant to 35 U.S.C. § 318(a) and
`37 C.F.R. § 42.73. For the reasons set forth below, we determine that
`Petitioners have shown by a preponderance of the evidence that the
`challenged claims are unpatentable. See 35 U.S.C. § 316(e).
`Additionally, we deny in part and dismiss in part the Motions to
`Exclude Evidence.
`
`Procedural History
`A.
`The original petitioner in this case was Mylan Pharmaceuticals, Inc.
`(“Petitioner Mylan”). Petitioner Mylan filed a Petition requesting an inter
`partes review of the challenged claims under 35 U.S.C. § 311. Paper 1
`(“Petition” or “Pet.”). Petitioner Mylan supported the Petition with the
`Declarations of Thomas Albini M.D. (Ex. 1002), and Mary Gerritsen Ph.D.
`(Ex. 1003). Regeneron Pharmaceuticals, Inc. (“Patent Owner”) filed a
`Preliminary Response to the Petition. Paper 10 (“Prelim. Resp.”). Patent
`Owner supported the Preliminary Response with the Declarations of Diana
`V. Do, M.D. (Ex. 2001). With our authorization, Paper 13, Petitioner Mylan
`filed a Reply to the Preliminary Response, and Patent Owner filed a Sur-
`reply to address further issues involving 35 U.S.C. § 325(d). Paper 16
`(“Reply”); Paper 19 (“Sur-reply”).
`On November 10, 2021, pursuant to 35 U.S.C. § 314, we instituted
`trial to determine whether any challenged claim of the ’338 patent is
`unpatentable based on the six grounds raised in the Petition:
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`2
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`32 U.S.C. § Reference(s)
`102
`Dixon2
`
`Adis3
`
`Regeneron 20084
`
`NCT-7955
`
`NCT-3776
`
`102
`
`102
`
`102
`
`102
`
`103
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`IPR2021-00881
`Patent 9,254,338 B2
`Claims Challenged
`1, 3–11, 13, 14, 16–24, 26
`
`1, 3–11, 13, 14, 16–24, 26
`
`1, 3–11, 13, 14, 16–24, 26
`
`1, 3–11, 13, 14, 16–24, 26
`
`1, 3–11, 13, 14, 16–24, 26
`
`1, 3–11, 13, 14, 16–24, 26
`
`Paper 21 (“Institution Decision” or “Inst. Dec.”).
`On February 9, 2022, we instituted an inter partes review in IPR2022-
`00258 and granted the motion for joinder with IPR2021-00881, adding
`Celltrion, Inc. as a petitioner in the instant proceeding. Paper 35. On the
`
`Dixon, Papadopoulos,7 Dix8
`
`
`2 James A. Dixon et al., “VEGF Trap-Eye for the treatment of neovascular
`age-related macular degeneration,” 18(10) Expert Opin. Investig. Drugs
`1573–1580 (2009) (Ex. 1006, “Dixon”)).
`3 Adis Data Information BV, “Aflibercept,” 9(4) Drugs R&D 261–269
`(2008) (Ex. 1007, “Adis”).
`4 Press Release, Regeneron, “Bayer and Regeneron Dose First Patient in
`Second Phase 3 Study for VEGF Trap-Eye in Wet Age-Related Macular
`Degeneration” (May 8, 2008) (Ex. 1013, “Regeneron 2008”).
`5 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of
`Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD)
`(VIEW1), NCT00509795, ClinicalTrials.gov (Apr. 28, 2009),
`https://clinicaltrials.gov/ct2/show/NCT00509795 (Ex. 1014, “NCT-795”).
`6 VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD
`(VIEW2), NCT00637377, ClinicalTrials.gov (Mar. 17, 2008),
`https://clinicaltrials.gov/ct2/show/NCT00637377 (Ex. 1015, “NCT-377”).
`7 Papadopoulos et al., US 7,374,758 B2, issued May 20, 2008, (Ex. 1010,
`“Papadopoulos”).
`8 Patent Application Publication No. 2006/0217311 A1 by Dix et al.,
`published Sep. 28, 2006 (Ex. 1033, “Dix”).
`
`3
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`same date, we also instituted an inter partes in IPR2022-00298 and likewise
`granted the motion for joinder with IPR2021-00881, adding Apotex, Inc. as
`a petitioner in the instant proceeding. Paper 36. Accordingly, we refer to
`Mylan Pharmaceuticals, Inc., Celltrion, Inc. and Apotex, Inc., collectively,
`as “Petitioners.”
`Patent Owner filed a Corrected Patent Owner Response to the
`Petition. Paper 41 (redacted, public version), Paper 40 (sealed version),
`(collectively, “PO Resp.”).9 Patent Owner supported the Patent Owner
`Response with the declarations of Diana V. Do, M.D. (Ex. 2001; Ex. 2051);
`Lucian V. Del Priore, M.D., Ph.D. (Ex. 2048 (sealed version); Ex. 2048
`(redacted, public version)); Alexander M. Klibanov, Ph.D. (Ex. 2049);
`David M. Brown, M.D. (Ex. 2050); Richard Manning, Ph.D. (Ex. 2052
`(sealed version); Ex. 2052 (public, redacted version)).
`Petitioners filed a Reply to the Patent Owner Response. Papers 61
`(sealed version), 62 (redacted, public version) (collectively, “Pet. Reply”).
`Petitioners supported the Reply with Supplemental Declarations from
`Dr. Albini (Ex. 1114) and Dr. Gerritsen (Ex. 1115), along with a Declaration
`from Dr. Hofmann (Ex. 1137) (sealed version), (Ex. 1137) (redacted, public
`version). Patent Owner filed a Sur-reply to Petitioners’ Reply. Paper 73
`(“PO Sur-reply”).
`Patent Owner and Petitioners each filed a Motion to Exclude
`Evidence. Papers 83 (“PO Mot.”), 81 (“Pet. Mot.”). Each party filed an
`Opposition to the corresponding motion. Papers 85 (“PO Opp.”), 84 (“Pet.
`
`
`9 In this Decision, we refer only to the public versions of papers and exhibits
`and not to confidential material.
`
`4
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`Opp.”). Each party also filed a Reply to the corresponding Opposition.
`Papers 86 (“PO Mot. Reply”), 87 (“Pet. Mot. Reply”).
`On August 10, 2022, the parties presented arguments at an oral
`hearing. Paper 78 (Order Granting Requests for Oral Hearing). The hearing
`transcript has been entered in the record. Paper 93 (“Tr.”).
`Real Parties-in-Interest
`B.
`Petitioner Mylan identifies itself, Viatris Inc., Mylan Inc., Momenta
`Pharmaceuticals, Inc., Janssen Research & Development LLC, and Johnson
`& Johnson as real parties-in-interest. Pet. 3, Paper 18 (Petitioner Mylan’s
`Amended Mandatory Notices). Petitioner Celltrion, Inc. identifies itself,
`Celltrion Healthcare Co. Ltd., and Celltrion Healthcare U.S.A., Inc. as real
`parties-in-interest. See IPR2022-00258, Paper 2, 3. Petitioner Apotex, Inc.
`identifies itself, Apotex Corp., Apotex Pharmaceutical Holdings Inc., and
`Aposherm Delaware Holdings Corp. as real parties-in-interest. See
`IPR2022-00298, Paper 1, 3. Patent Owner identifies itself as the real party-
`in-interest. Paper 5, 2.
`
`Related Proceedings
`C.
`Petitioners and Patent Owner identify Mylan Pharms. Inc. v.
`Regeneron Pharms., Inc., IPR2021-00880 (PTAB May 5, 2021) (“the -880
`IPR”) as a related matter. Pet. 3; Paper 5, 2. The -880 IPR challenges
`claims 1 and 8–12 of U.S. Patent No. 9,669,069 B2 (“the ’069 patent”). The
`parties further identify Chengdu Kanghong Biotechnol. Co. v. Regeneron
`Pharms., Inc., PGR2021-00035 (petition dismissed and proceeding
`terminated, Paper 8 (PTAB June 25, 2021)) challenging the claims of
`U.S. Patent No. 10,828,345 B2 (“the ’345 patent”), which is related to the
`’338 patent and the ’069 patent. Pet. 4; Paper 5, 2.
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`Petitioners identify additional patents and patent applications that
`claim priority to the ’338 patent, namely: U.S. Patent Nos. 10,130,681 B2,
`10,857,205 B2, 10,828,345 B2, and 10,888,601 B2; and U.S. Application
`Serial Nos. 17/072,417, 17/112,063, and 17/112,404. Pet. 4.
`The ’338 Patent
`D.
`The ’338 patent relates to methods for treating angiogenic eye
`disorders. Ex. 1001, 1:63–64. Angiogenic eye disorders include age-related
`macular degeneration (“AMD”) and diabetic macular edema (“DME”). Id.
`at 1:24–34. According to the Specification, “[r]elease of vascular
`endothelial growth factor (VEGF) contributes to increased vascular
`permeability in the eye and inappropriate new vessel growth. Thus,
`inhibiting the angiogenic-promoting properties of VEGF appears to be an
`effective strategy for treating angiogenic eye disorders.” Id. at 1:44–48.
`The Specification describes inhibiting the angiogenic-promoting
`properties of VEGF by administering a VEGF antagonist. Id. at 4:37–42.
`VEGF antagonists may include “VEGF receptor-based chimeric
`molecule(s), (also referred to herein as a ‘VEGF-Trap’ or ‘VEGFT’). An
`exemplary VEGF antagonist . . . is a multimeric VEGF-binding protein
`comprising two or more VEGF receptor-based chimeric molecules referred
`to herein as ‘VEGFR1R2-Fc[Δ]C1(a)’ or ‘aflibercept.’” Id. at 2:30–37.
`“VEGFR1R2-FcΔC1(a) comprises three components: (1) a VEGFR1
`component comprising amino acids 27 to 129 of SEQ ID NO:2; (2) a
`VEGFR2 component comprising amino acids 130 to 231 of SEQ ID NO:2;
`and (3) a multimerization component [] comprising amino acids 232 to 457
`of SEQ ID NO:2.” Id. at 4:58–5:3 (citing U.S. Patent No. 7,396,664 B2).
`The Specification discloses that, despite the known methods for
`treating eye disorders using VEGF antagonists, “there remains a need in the
`
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`IPR2021-00881
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`art for new administration regimens for angiogenic eye disorders, especially
`those which allow for less frequent dosing while maintaining a high level of
`efficacy.” Id. at 1:53–61. The Specification discloses that
`[t]he present inventors have surprisingly discovered that
`beneficial therapeutic effects can be achieved in patients
`suffering from angiogenic eye disorders by administering a
`VEGF antagonist to a patient at a frequency of once every 8 or
`more weeks, especially when such doses are preceded by about
`three doses administered to the patient at a frequency of about 2
`to 4 weeks.
`Id. at 2:3–10. The Specification describes this dosing regimen as
`sequentially administering initial, secondary, and tertiary doses. See id. at
`1:62–2:3. The Specification refers to “sequentially administering” as “each
`dose of VEGF antagonist is administered to the patient at a different point in
`time, e.g., on different days separated by a predetermined interval (e.g.,
`hours, days, weeks or months).” Id. at 3:22–26. The Specification refers to
`the “initial dose” as “the dose which is administered at the beginning of the
`treatment regimen;” the “secondary doses” as “the doses which are
`administered after the initial dose;” and the “tertiary doses” as “the doses
`which are administered after the secondary doses.” Id. at 3:31–38.
`
`Illustrative Claims
`E.
`Petitioners challenge claims 1, 3–11, 13, 14, 16–24 and 26 of the ’338
`patent. Claims 1 and 14, the only independent claims, are set forth below as
`illustrative of the claimed subject matter.
`1. A method for treating an angiogenic eye disorder in a
`patient, said method comprising sequentially 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;
`
`7
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`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;
`wherein the VEGF antagonist is a VEGF receptor-based
`chimeric molecule comprising (1) a VEGFR1 component
`comprising amino acids 27 to 129 of SEQ ID NO:2; (2) a
`VEGFR2 component comprising amino acids 130–231 of
`SEQ ID NO:2; and (3) a multimerization component
`comprising amino acids 232–457 of SEQ ID NO:2.
`Ex. 1001, 23:2–18.
`14. A method for treating an angiogenic eye disorder in a
`patient, said method comprising sequentially 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;
`wherein the VEGF antagonist is a VEGF receptor-based
`chimeric molecule comprising VEGFR1R2-FcΔC1(a)
`encoded by the nucleic acid sequence of SEQ ID NO:1.
`Id. at 24:2–15.
`
`II.
`
`PATENTABILITY ANALYSIS
`Principles of Law
`A.
`To prevail in its challenges to the patentability of all claims of the
`’338 patent, Petitioners must demonstrate by a preponderance of the
`evidence that the claims are unpatentable. 35 U.S.C. § 316(e); 37 C.F.R.
`§ 42.1(d) (2019). “In an [inter partes review], the petitioner has the burden
`from the onset to show with particularity why the patent it challenges is
`unpatentable.” Harmonic Inc. v. Avid. Tech., Inc., 815 F.3d 1356, 1363
`
`8
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`(Fed. Cir. 2016); see also 35 U.S.C. § 312(a)(3) (2012) (requiring inter
`partes review petitions to identify “with particularity . . . the evidence that
`supports the grounds for the challenge to each claim”). That burden of
`persuasion never shifts to Patent Owner. Dynamic Drinkware, LLC v. Nat’l
`Graphics, Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015); see also In re
`Magnum Oil Tools Int’l, Ltd., 829 F.3d 1364, 1375–78 (Fed. Cir. 2016)
`(discussing the burden of proof in inter partes review).
`“A claim is anticipated only if each and every element as set forth in
`the claim is found, either expressly or inherently described, in a single prior
`art reference.” Schering Corp. v. Geneva Pharms, 339 F.3d 1373 (Fed. Cir.
`2003) (quoting Verdegaal Bros., Inc. v. Union Oil Co. of Cal., 814 F.2d 628,
`631 (Fed. Cir. 1987)). It is well settled that “a reference can anticipate a
`claim even if it ‘d[oes] not expressly spell out’ all the limitations arranged or
`combined as in the claim, if a person of skill in the art, reading the reference,
`would ‘at once envisage’ the claimed arrangement or combination.”
`Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed.
`Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681 (1962)).
`Level of Ordinary Skill in the Art
`B.
`The level of skill in the art is a factual determination that provides a
`primary guarantee of objectivity in an obviousness analysis. Al-Site Corp. v.
`VSI Int’l Inc., 174 F.3d 1308, 1323 (Fed. Cir. 1999) (citing Graham v. John
`Deere Co., 383 U.S. 1, 17–18 (1966)); Ryko Mfg. Co. v. Nu-Star, Inc.,
`950 F.2d 714, 718 (Fed. Cir. 1991)).
`Petitioners assert that a person of ordinary skill in the art at the time of
`the invention would have had
`(1) knowledge regarding the diagnosis and treatment of
`angiogenic eye disorders, including the administration of
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`therapies to treat said disorders; and (2) the ability to understand
`results and findings presented or published by others in the field,
`including the publications discussed herein. Typically, such a
`person would have an advanced degree, such as an M.D. or Ph.D.
`(or equivalent, or less education but considerable professional
`experience in the medical, biotechnological, or pharmaceutical
`field), with practical academic or medical experience in
`(i) developing treatments for angiogenic eye disorders (such as
`AMD), including through the use of VEGF antagonists, or
`(ii) treating of same, including through the use of VEGF
`antagonists.
`Pet. 22 (citing Ex. 1002 ¶¶ 26–28; Ex. 1003 ¶¶ 20–24).
`In the Patent Owner Response, Patent Owner asserts in a footnote that
`it disagrees with Petitioners’ definition of the person having ordinary skill in
`the art (“POSA”). PO Resp. 15 n.7. According to Patent Owner, “the POSA
`is an ophthalmologist with experience in treating angiogenic eye disorders,
`including through the use of VEGF antagonists.” Id. (citing Ex. 2051 ¶ 28).
`According to Dr. Do, “only an ophthalmologist would have the firsthand
`experience of diagnosing and treating angiogenic eye disorders to which the
`patent is plainly directed.” Ex. 2051 ¶ 28. Patent Owner, however, asserts
`that it “does not believe that parties[’] differing definitions of ‘the POSA’
`matter for any argument in [the] Patent Owner Response.” PO Resp. 15 n.7.
`Having considered the arguments and evidence, we maintain that
`Petitioners’ definition of one of ordinary skill in the art is reasonable and
`consistent with the ’338 patent and the prior art of record. On the other
`hand, we find Patent Owner’s definition to be inappropriately limited to
`those having “firsthand experience” regarding the diagnosis and treatment of
`angiogenic eye disorders, as explained by Dr. Do. See Ex. 2051 ¶ 28. While
`it may be that the claimed methods would be performed an ophthalmologist,
`a person having ordinary skill in the art need not be limited to those
`
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`performing the claimed method. Rather, we find that Petitioners’ definition
`more appropriately considers that knowledge regarding the diagnosis and
`treatment of angiogenic eye disorders, including the administration of
`therapies to treat said disorders, may be possessed by other professionals
`that are not ophthalmologists. Accordingly, we adopt Petitioners’ definition
`for purposes of this Decision.
`We have reviewed the credentials of Petitioners’ declarants, Drs.
`Albini and Gerritsen, and Patent Owner’s declarants, Drs. Do, Del Priore,
`Klibanov, Brown, and Manning, and consider each of them to be qualified to
`provide the opinions for which their testimony has been submitted.
`Claim Construction
`C.
`The Board applies the same claim construction standard that would be
`used to construe the claim in a civil action under 35 U.S.C. § 282(b).
`37 C.F.R. § 100(b) (2019). Under that standard, claim terms “are generally
`given their ordinary and customary meaning” as understood by a person of
`ordinary skill in the art at the time of the invention. Phillips v. AWH Corp.,
`415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc) (quoting Vitronics Corp.
`v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). “In determining
`the meaning of the disputed claim limitation, we look principally to the
`intrinsic evidence of record, examining the claim language itself, the written
`description, and the prosecution history, if in evidence.” DePuy Spine, Inc.
`v. Medtronic Sofamor Danek, Inc., 469 F.3d 1005, 1014 (Fed. Cir. 2006)
`(citing Phillips, 415 F.3d at 1312–17).
`Petitioners and Patent Owner propose constructions for certain claim
`terms. See Pet. 11–22; PO Resp. 7–24. In the following discussion, we
`address those proposed constructions.
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`“A method for treating an angiogenic eye disorder in a patient”
`1.
`At the institution stage, we made a preliminary finding that the
`preambles of claims 1 and 14, i.e., “[a] method for treating an angiogenic
`eye disorder in a patient,” are limiting. Inst. Dec. 18. We also determined
`preliminarily that the claimed methods do not require any “specific degree of
`efficacy.” Id. at 20–21. In the following discussion, we address the parties’
`arguments and our final claim construction for this phrase.
`Petitioners’ Position
`a)
`According to Petitioners, “[t]he ‘method for treating’ preamble of
`independent claims 1 and 14 is ‘merely a statement of purpose or intended’
`use for the claimed dosing regimen(s) and is non-limiting.” Pet. 17 (citing
`Bristol-Myers Squibb Co. v. Ben Venue Lab’ys, Inc., 246 F.3d 1368, 1375
`(Fed. Cir. 2001)). Petitioners further assert that the preamble provides no
`antecedent basis for any other claim element, nor results in a manipulative
`difference in the steps of the claims. Id. at 20 (citing In re Copaxone
`Consol. Cases, 906 F.3d 1013, 1023 (Fed. Cir. 2018)).
`Petitioners assert that even if the preamble is limiting, the plain and
`ordinary meaning of the “method of treating an angiogenic eye disorder”
`does not require a therapeutically effective treatment. Id. at 20. Rather,
`Petitioners assert that the plain and ordinary meaning merely requires
`“administering a therapeutic to a patient, without a specific degree of
`efficacy required.” Id. at 20–21 (citing, Ex. 1002 ¶ 43).
`Patent Owner’s Response
`b)
` Patent Owner asserts that “the claimed ‘method for treating’ must
`actually treat, not merely intend to treat” because the preamble reciting a
`method for treating “is a positive limitation of the claim that must be
`practiced to satisfy the claim.” PO Resp. 9. Further, Patent Owner asserts
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`that “the claimed method for treating requires treatment of a patient with a
`high level of efficacy, on par with the prevailing standard-of-care at the time
`of filing.” Id. at 13 (citing Ex. 2051 ¶¶ 54–84). In support of that position,
`Patent Owner relies on the results of Regeneron’s Phase III studies, which
`Patent Owner asserts “shows that a similar proportion of subjects in each of
`the VEGF Trap-Eye dosing arms, including the Q8 dosing arm, met the
`primary endpoint of loss of ≤15 letters on ETDRS[10] (95.1% or 95.6%) as
`compared to monthly ranibizumab (94.4%)” and “reports similar mean
`improvement in vision as compared to monthly ranibizumab, with an
`average gain of 7 or more letters for the Q8 dosing regimen.” Id. at 14–15
`(citing Ex. 1001, 14:3–23 (Table 1)). According to Patent Owner, a POSA
`would have concluded from the study data that “VEGF Trap-Eye, including
`on a Q8 dosing schedule, achieved and maintained a high level of efficacy
`that was non-inferior to standard-of-care Lucentis.” Id. at 15.
`Patent Owner also contends that the prosecution history confirms that
`the claimed treatment methods must achieve a high level of efficacy because
`“Regeneron relied on Heier 2012 (Ex. 1018) to overcome a double patenting
`rejection by arguing that the ‘treatment protocol’ encompassed by the
`claimed invention resulted in surprising efficacy, i.e., noninferiority to
`ranibizumab, despite less frequent dosing than the standard of care) i.e.,
`monthly dosing of ranibizumab).” Id. at 16 (citing Ex. 1017, 288–91, 315).
`Further, Patent Owner argues that “the POSA would have understood
`that a less frequent dosing regimen that was inferior to the standard-of-care,
`or worse yet—ineffective—would not have been viewed as treatment by
`2011.” Id. at 17. In support of that position, Patent Owner asserts that
`
`
`10 Early Treatment Diabetic Retinopathy Study (“ETDRS”).
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`although another medication, Macugen, “demonstrated some level of
`efficacy” by slowing vision loss with a recommended dosing schedule of
`once every 6 weeks, “once Lucentis was approved and showed that it could
`restore vision, no one considered Macugen to be effective treatment and
`practitioners stopped using it.” Id. at 17. According to Patent Owner, that
`example demonstrates that “the POSA would have understood what the ’338
`Patent makes explicit—that the claimed ‘method for treating’ must provide
`highly effective treatment (non-inferior to the standard-of-care at the time of
`patent filing) to the patient.” Id. at 17–18 (citing Ex. 2051 ¶¶ 46–84).
`Additionally, Patent Owner asserts that the claims do not encompass
`“ineffective treatment methods, such as the administration of
`non-therapeutically effective dose amounts,” because methods that are not
`“therapeutically effective” “would not be ‘treatment’ as the term is
`understood by the POSA.” Id. at 19–20 (citing Ex. 2051 ¶¶ 47–53).
`Patent Owner also challenges Petitioners’ contention that the ’338
`patent only requires a patient to exhibit a loss of fifteen or fewer letters on
`the ETDRS visual acuity chart within 104 weeks of treatment initiation. Id.
`at 20–21 (citing Pet. 21). Patent Owner argues that “the POSA would not
`have considered such loss of ≤15 letters on ETDRS to reflect an effective
`method for treating an angiogenic eye disorder by 2011.” Id. at 21.
`According to Patent Owner, the POSA would have understood that a loss of
`fifteen or fewer letters or a gain of letters on ETDRS are “common clinical
`trial endpoints [that] are used to measure results of angiogenic eye disorder
`treatments in the art, and in the ’338 Patent specification.” Id. at 21. Patent
`Owner contends that those clinical trial endpoints were “not to define an
`outcome that reflects an effective treatment method.” Id.
`
`14
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`Petitioners’ Reply
`c)
`In the Reply, Petitioners maintain that the preamble is not limiting,
`but rest on their arguments in the Petition regarding that issue. Pet. Reply 7.
`Petitioners explain that for the remainder of the Reply arguments, Petitioners
`apply the Board’s preliminary holding that the preamble is limiting. Id.
`Petitioners maintain also that, if limiting, the preamble should be
`afforded its plain and ordinary meaning, i.e., “administering a therapeutic
`agent to a patient, without a specific degree of efficacy required.” Id. (citing
`Ex. 1002 ¶ 43). Petitioners assert that Patent Owner’s proposed construction
`“necessitates reading-in the ‘high level of efficacy’ concept [into the
`claims]—‘one of the cardinal sins of patent law.’” Id. at 8 (quoting SciMed
`Life Sys., Inc. v. Advanced Cardiovascular Sys., Inc., 242 F.3d 1337, 1340
`(Fed. Cir. 2001)). Petitioners contend that “[t]he Claims as-written
`inherently encompass all levels of efficacy not just a ‘high’ one.” Id. at 9.
`According to Petitioners, the Specification does not include any clear
`disavowal in that regard. Id. at 10.
`Petitioners note that although the claims do not recite the term
`“efficacy,” the Specification defines the term by stating:
` “efficacy” means that, from the initiation of treatment, the
`patient exhibits a loss of 15 or fewer letters on the [ETDRS]
`visual acuity chart. In certain embodiments, “efficacy” means a
`gain of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or more)
`letters on the ETDRS chart from the time of initiation of
`treatment.
` Id. at 10–11 (quoting Ex. 1001, 7:24–32). Petitioners assert that if the term
`“efficacy” is incorporated within the claims, it would require, “at most, a
`patient exhibit a loss of fifteen or fewer letters on the ETDRS visual acuity
`chart within 104 weeks of treatment initiation.” Id. at 11 (citing Ex. 1002
`
`15
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`¶ 43). Petitioners contend that “[t]he specification nowhere defines or
`guides how a POSA should ascertain, measure, or differentiate a ‘high level
`of efficacy.’” Id. (citing Ex. 1114 ¶¶ 30–40). Petitioners assert further that
`Patent Owner has not demonstrated what actually constitutes “‘non-
`inferiority’ for each ‘standard of care’ (e.g., a BCVA score), and how a
`POSA could assess that with reasonable certainty.” Id. at 13–14 (citing
`Ex. 1114 ¶¶ 30–40).
`
`Patent Owner’s Sur-reply
`d)
`In the Sur-reply, Patent Owner continues to urge that the intrinsic
`record supports construing the preambles of claims 1 and 14 such that
`“treat” means “achieving a high level of efficacy.” PO Sur-reply 4. In
`particular, Patent Owner alleges that the Specification and the prosecution
`history refer to: (a) the changed state-of-art; (b) an expectation of efficacy
`comparable to the “high level of efficacy” achieved with existing ranizumab
`treatment; and (c) a distinction between the claimed regimens from extended
`dosing regimens in the art that result in visual acuity losses. Id. at 5.
`According to Patent Owner, “[i]n view of the high level of efficacy that was
`expected of anti-VEGF therapies in the art, nothing more is needed” to
`support construing the claims to require the same high level of efficacy. Id.
`In response to Petitioners’ assertion that the Specification defines
`“efficacy” as “a loss of 15 or fewer letters” on the ETDRS visual acuity
`chart, Patent Owner asserts that “lexicography is inapplicable.” Id. at 7–8.
`In support of that position, Patent Owner states that “it is undisputed that (1)
`‘efficacy’ is not a claim limitation for construction; and (2) the specification
`provides no express definition for ‘treating’ or ‘treatment.’” Id. Further,
`Patent Owner asserts that “it is undisputed that ‘the POSA would not have
`considered a loss of ≤15 letters on ETDRS’ to reflect the level of efficacy
`
`16
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`expected for a method for treating angiogenic eye disorders by 2011.” Id.
`at 9. According to Patent Owner, “the POSA would know with reasonable
`certainty that, by 2011, a highly effective treatment for angiogenic eye
`disorders is one that is on par to Lucentis or off-label Avastin and can
`produce visual acuity gains, not just slow vision losses.” Id. at 11 (citing
` Ex. 2050 ¶¶ 84, 99).
`
`Discussion
`e)
`Having considered the record as a whole, we determine that the
`preamble of method claims 1 and 14, i.e., “[a] method for treating an
`angiogenic eye disorder in a patient” is limiting. Although we agree with
`Petitioners that the preamble sets forth “‘a statement of purpose or intended’
`use for the claimed dosing regimen,” see Pet. 17, that does not the end our
`inquiry. As noted in the Institution Decision, the Federal Circuit has
`explained that its case law does not support a “binary distinction between
`statements of mere intended purpose on the one hand and limiting preambles
`on the other.” Eli Lilly and Company v. Teva Pharms. Int’l GmbH, 8 F.4th
`1331, 1340 (Fed. Cir. 2021). Rather, as the Federal Circuit reiterated, “there
`is no ‘litmus test’ for determining whether a preamble is limiting.” Id.
`(citing Bicon, Inc. v. Straumann Co., 441 F.3d 945, 952 (Fed. Cir. 2006) and
`Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 808 (Fed.
`Cir. 2002)). As the Court instructed, we consider whether to treat a
`preamble as a claim limitation based upon “the facts [in this] case in light of
`the claim as a whole and the invention described in the patent.” Id. (quoting
`Storage Tech. Corp. v. Cisco Sys., Inc., 329 F.3d 823, 831 (Fed. Cir. 2003)).
`Here, the claims are directed to methods of administering, i.e., using,
`a VEGF antagonist for an intended purpose of “treating an angiogenic eye
`disorder in a patient.” See Claims 1 and 14, Ex. 1001, 23:2–3; 24:3–4. The
`
`17
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`Specification repeatedly characterizes the method as one for treating
`angiogenic eye disorders in patients. See, e.g., id. at 1:18–20, 63–66, 2:23–
`27; 3:19–20; 5:11–13. Apart from the preamble, the independent claims do
`not elsewhere recite or indicate any other use for the method steps
`comprising the administration of a VEGF antagonist. Thus, we determine
`that the preamble sets forth the essence of the invention—treating an
`angiogenic eye disorder in a patient. As the Federal Circuit explained in
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d
`1339 (Fed. Cir. 2003), “preamble language will limit the claim if it recites
`not merely a context in which the invention may be used, but the essence of
`the invention without which performance of the recited steps is nothing but
`an academic exercise,” and that this principle frequently holds true for
`method claims. Id. at 1345 (citing Griffin