Trials@uspto.gov
`571.272.7822
`
`Paper 9
`Entered: March 10, 2023
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`APOTEX INC.,
`Petitioner,
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`____________
`
`IPR2022-01524
`Patent 11,253,572 B2
`____________
`
`Before SUSAN L. C. MITCHELL, ROBERT A. POLLOCK, and
`RYAN H. FLAX, Administrative Patent Judges.
`
`FLAX, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314
`
`Samsung Bioepis Exhibit 1004
`Page 1
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`INTRODUCTION
`I.
`Regeneron Pharmaceuticals, Inc. (“Patent Owner”) is the owner of
`U.S. patent 11,253,572 B2 (“the ’572 patent”). Paper 5, 1. On September 9,
`2022, Apotex Inc. (“Petitioner”) filed a Petition for inter partes review
`challenging the patentability of claims 1–14 and 26–30 of the ’572 patent
`(claims 15–25 are not challenged). Paper 1, 1 (“Pet.”). On December 23,
`2022, Patent Owner filed a Preliminary Response to the Petition. Paper 7
`(“Prelim. Resp.”). No further briefing was requested or authorized.
`Under 37 C.F.R. § 42.4(a), we have authority to determine whether to
`institute trial in an inter partes review. We may institute an inter partes
`review if the information presented in the petition filed under 35 U.S.C.
`§ 311, and any preliminary response filed under § 313, shows that there is a
`reasonable likelihood that Petitioner would prevail with respect to at least
`one of the claims challenged in the petition. 35 U.S.C. § 314.
`After reviewing the parties’ submissions, we conclude Petitioner does
`not demonstrate a reasonable likelihood it would prevail in showing that any
`challenged claim of the ’572 patent is unpatentable under the presented
`grounds. Therefore, we deny institution of inter partes review. 1 Our
`reasoning is discussed below.
`A. REAL PARTIES-IN-INTEREST
`Petitioner lists Apotex Inc., Apotex Corp, Apotex Pharmaceutical
`Holdings Inc, and Aposherm Delaware Holdings Corp. as real parties-in-
`
`
`1 We note that there are disputed issues in this proceeding under 35 U.S.C.
`§ 325(d) and § 314(a). See Pet. 6–11; Prelim. Resp. 47–57. However,
`because we determine institution should be denied on the merits, we do not
`address these matters.
`
`2
`
`Samsung Bioepis Exhibit 1004
`Page 2
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`interest. Pet. 2. Patent Owner identifies itself as the only real
`party-in-interest. Paper 5, 1.
`B. RELATED MATTERS
`Petitioner identifies the following as related matters: IPR2021-00881
`(concerning U.S. Patent 9,254,338 (“the ’338 patent”); IPR2022-00258 (also
`concerning the ’338 patent); IPR2022-00298 (also concerning the ’338
`patent); IPR2021-00880 (concerning U.S. Patent 9,669,069 (“the ’069
`patent)); IPR2022-0257 (also concerning the ’069 patent); IPR2022-00301
`(also concerning the ’069 patent); IPR2022-01225 (concerning U.S. Patent
`10,130,681 (“the ’681 patent”); and IPR2022-01226 (concerning U.S. Patent
`10,888,601 (“the ’601 patent”). Pet. 3–4. Petitioner also identifies as related
`Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No. 1:22-cv-00061-TSK
`(N.D. W.Va), and PGR2021-00035 (concerning U.S. Patent 10,828,345).
`Id. at 5. In addition to the above-listed patents, Petitioner identifies U.S.
`Patent Application Nos. 17/072,417; 17/112,404; 17/112,063; and
`17/350,958 as related. Id. Patent Owner identifies the same matters,
`patents, and applications as related. Paper 5, 2–3.
`THE ’572 PATENT
`C.
`The ’572 patent issued on February 22, 2022, from U.S. Application
`17/352,892, which was filed on June 21, 2021. Ex. 1001, codes (45), (21),
`(22). The ’572 patent ultimately indicates priority to U.S. Provisional
`Application 61/432,245, filed on January 13, 2011. Id. at code (60), 1:7–29.
`Petitioner declines to challenge whether the ’572 patent is entitled such
`priority. See, e.g., Pet. 1 (“Long before the patent’s alleged 2011 priority
`date . . . .”).
`
`3
`
`Samsung Bioepis Exhibit 1004
`Page 3
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`The ’572 patent’s abstract states:
`The present invention provides methods for treating angiogenic
`eye disorders by sequentially administering multiple doses of a
`VEGF antagonist to a patient. The methods of the present
`invention include the administration of multiple doses of a
`VEGF antagonist to a patient at a frequency of once every 8 or
`more weeks. The methods of the present invention are useful
`for the treatment of angiogenic eye disorders such as age related
`macular degeneration, diabetic retinopathy, diabetic macular
`edema, central retinal vein occlusion, branch retinal vein
`occlusion, and corneal neovascularization.
`Id. at Abstract.
`As background, the ’572 patent states that “[r]elease of vascular
`endothelial growth factor (VEGF) contributes to increased vascular
`permeability in the eye and inappropriate new vessel growth,” and
`“inhibiting the angiogenic-promoting properties of VEGF appears to be an
`effective strategy for treating angiogenic eye disorders.” Id. at 1:60–65. As
`further background, the ’572 patent identifies that “FDA-approved
`treatments of angiogenic eye disorders such as AMD and CRVO include the
`administration of an anti-VEGF antibody called ranibizumab (Lucentis®,
`Genentech, Inc.) on a monthly basis by intravitreal injection.” Id. at 1:66–
`2:2. The ’572 patent indicates that its invention is a response to the need for
`“new administration regimes” of “less frequent dosing while maintaining a
`high level of efficacy.” Id. at 2:6–9.
`In summarizing its invention, the ’572 patent states:
`The 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
`
`4
`
`Samsung Bioepis Exhibit 1004
`Page 4
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`to 4 weeks. Thus, according to the methods of the present
`invention, each secondary dose of VEGF antagonist is
`administered 2 to 4 weeks after the immediately preceding
`dose, and each tertiary dose is administered at least 8 weeks
`after the immediately preceding dose.
`Id. at 2:22–33. Relating to this, the ’572 patent defines certain terms. For
`example, “the VEGF antagonist comprises one or more VEGF receptor-
`based chimeric molecule(s), (also referred to herein as a ‘VEGF-Trap’ or
`‘VEGFT’),” and an example of this includes a product called “aflibercept,”
`marketed as “EYLEA” by Regeneron Pharmaceuticals, Inc. and approved by
`the FDA in November 2011 at a dose of 2 mg via intravitreal injection
`every 4 weeks for three months and then every 8 weeks. Id. at 2:47–67.
`On the aforementioned FDA-approved dosing regimen, the ’572
`patent further defines the terms (ultimately used in the claims) “initial dose,
`“secondary doses,” and “tertiary doses” as follows:
`the “initial dose” is the dose which is administered at the
`beginning of the treatment regimen (also referred to as the
`“baseline dose”); the “secondary doses” are the doses which are
`administered after the initial dose; and the “tertiary doses” are
`the doses which are administered after the secondary doses.
`Id. at 3:51–58.
`The ’572 patent describes a series of Examples detailing clinical trials
`conducted to validate the VEGFT drug and the dosing regimen. Id. at 8:12–
`18:3. Example 4 details two “Phase III Clinical Trials of the Efficacy,
`Safety, and Tolerability of Repeated Doses of Intravitreal VEGFT in
`Subjects with Neovascular Age-Related Macular Degeneration” (AMD)
`(Study 1 and Study 2), which followed dosing regimens using 2 mg doses of
`aflibercept at the aforementioned initial dose, then two 4-week doses, and
`then doses every 8-weeks through the end of the 52-week study (the “2Q8”
`
`5
`
`Samsung Bioepis Exhibit 1004
`Page 5
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`regimen). Id. at 9:29–14:30. The results of this and other regimens were
`compared to subjects administered 0.5 mg ranibizumab every 4 weeks (the
`“RQ4” regimen) by assessing patients’ visual acuity based on a Best
`Corrected Visual Acuity (BCVA) test, which is based on the ability to
`identify letters. Id. at 9:35–10:7. This disclosure describes the inclusion
`criteria and exclusion criteria for the participating patients. Id. at 10:50–
`12:22.
`Results of the Example 4 clinical trials are described in TABLE 1,
`which we reproduce below:
`
`
`
`Id. at 13:9–27. The ’572 patent describes that these results showed that the
`VEGFT therapies usually maintained or improved visual acuity in patients
`and were not inferior to the ranibizumab treatment based on similar criteria.
`Id. at 13:28–38.
`
`6
`
`Samsung Bioepis Exhibit 1004
`Page 6
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`As Example 5, the ’572 patent describes a phase 2 clinical trail using
`the same drug, also administered at 2 mg doses and, in one arm, at a regimen
`of three initial doses every four weeks followed by doses every eight weeks,
`but treating patients with diabetic macular edema (DME). Id. at 14:32–15:5.
`The ’572 patent describes that visual acuity in this trial was maintained or
`improved for all VEGFT study groups. Id.
`The ’572 patent concludes with 30 claims, of which claims 1, 15 (not
`challenged), 26, and 29 are independent claims. Ex. 1012, 62:12–64:20.
`Claim 1 is illustrative and reproduced below:
`1. A method of treating an angiogenic eye disorder in a
`patient in need thereof comprising sequentially administering to
`the patient by intravitreal injection a single initial dose of 2 mg
`of aflibercept, followed by one or more secondary doses of
`2 mg of aflibercept, followed by one or more tertiary doses of
`2 mg of aflibercept;
`wherein each secondary dose is administered
`approximately 4 weeks following the immediately
`preceding dose; and
`wherein each tertiary dose is administered
`approximately 8 weeks following the immediately
`preceding dose;
`wherein the patient achieves a gain in visual acuity
`within 52 weeks following the initial dose.
`Ex. 1001, 23:2–14.
`Independent claim 26 is similar to claim 1 in reciting the same drug, at
`the same dose, and administered the same way, on the same schedule, but
`adds that the method treats “age related macular degeneration” (AMD) and
`that “the method is as effective in achieving a gain in visual acuity as
`monthly administration of 0.5 mg of ranibizumab by intravitreal injection in
`human subjects with age-related macular degeneration at 52 weeks
`
`7
`
`Samsung Bioepis Exhibit 1004
`Page 7
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`following the initial dose.” Id. at 24:26–44. Independent claim 29 is also
`similar to claim 1, and essentially the same as claim 26, but differs in
`requiring effectiveness in “maintaining visual acuity” rather than a gain
`therein. Id. at 24:50–67.
`D. ASSERTED GROUNDS FOR UNPATENTABILITY
`Petitioner asserts the following grounds for the unpatentability of
`claims 1–14 and 26–30 of the ’572 patent:
`
`
`Reference(s)/Basis
`Dixon3
`Regeneron 20084
`NCT-7955
`NCT-3776
`
`Ground Claims Challenged 35 U.S.C. §2
`1
`1–5, 8–11, 14, 26–30
`102
`2
`1–5, 8–11, 14, 26–30
`102
`3
`1–5, 8–11, 14, 26–30
`102
`4
`1–5, 8–11, 14, 26–30
`102
`
`2 The ’572 patent has an uncontested January 13, 2011, priority date, which
`is before the AIA revisions to 35 U.S.C. §§ 102 and 103 took effect on
`March 16, 2013. 35 U.S.C. § 100 (note). Therefore, pre-AIA §§ 102 and
`103 apply. Our decision is not impacted by which version of the statute
`applies.
`3 James A. Dixon et al., VEGF Trap-Eye for the treatment of neovascular
`age-related macular degeneration, 18(10) EXPERT OPIN. INVESTIG. DRUGS
`1573–80 (2009) (Ex. 1006, “Dixon”).
`4 Regeneron, News Release: Bayer and Regeneron Dose First Patient in
`Second Phase 3 Study for VEGF Trap-Eye in Wet Age-Related Macular
`Degeneration -International study to evaluate efficacy and safety in treating
`a leading cause of blindness 1–3 (May 8, 2008) (Ex. 1009, “Regeneron
`2008”).
`5 NIH, U.S. National Library of Medicine, ClinicalTrials.gov archive,
`History of Changes for Study: NCT00509795, Vascular Endothelial Growth
`Factor(VEGF)Trap-Eye:Investigation of Efficacy and Safety in Wet Age-
`Related Macular Degeneration(AMD) (VIEW1) (Dec. 20, 2012), accessed
`January 7, 2021, at https://clinicaltrials.gov/ct2/history/NCT00509795?A
`=8&B=9&C=merged#StudyPageTop (Ex. 1010, “NCT-795”).
`6 NIH, U.S. National Library of Medicine, ClinicalTrials.gov archive,
`History of Changes for Study: NCT00637377, VEGF Trap-Eye:
`
`8
`
`Samsung Bioepis Exhibit 1004
`Page 8
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`Ground Claims Challenged 35 U.S.C. §2
`5a7
`6, 7, 12, 13
`103
`5b
`6, 7, 12, 13
`103
`5c
`6, 7, 12, 13
`103
`5d
`6, 7, 12, 13
`103
`
`Reference(s)/Basis
`Dixon, Hecht8
`Regeneron 2008, Hecht
`NCT-795, Hecht
`NCT-377, Hecht
`
`
`See Pet. 12.
`In support of these grounds for unpatentability Petitioner submits,
`inter alia, the Declaration of Angelo P. Tanna, MD (Ex. 1002). In the
`absence of evidence to the contrary, we find Dr. Tanna competent to testify
`on the subject matter of his declaration. See infra Section II.A; see Ex. 1002
`¶¶ 3–11, 15–18; Ex. 1003. We understand that Patent Owner has not
`submitted a similar witness declaration specifically directed to this
`proceeding, nor was it required to do so. Patent Owner has, however,
`submitted witness declarations from related proceedings before the Board,
`including the Declaration of Lucian V. Del Priore, MD, PhD, which was
`submitted in related matters IPR2021-00880 and IPR2021-00881 (and notes
`that IPR2022-00257, IPR2022-00258, IPR2022-00298, and IPR2022-00301
`were joined therewith). See Ex. 2021; see also Prelim. Resp. viii, 37, 40; see
`
`
`Investigation of Efficacy and Safety in Wet AMD (VIEW 2) (Nov. 28, 2014),
`accessed Dec. 29, 2020, at https://clinicaltrials.gov/ct2/history/
`NCT00637377?A =1&B=1&C=merged#StudyPageTop (Ex. 1011,
`“NCT-377”).
`7 Grounds 5a–5d listed here are presented by Petitioner as a single
`“Ground 5”; however, because that ground actually asserts four separate
`challenges for unpatentability premised on separate combinations of the
`references of Grounds 1–4 in combination with Hecht, we separate these
`into separate grounds.
`8 Gerald Hecht, PhD, Ophthalmic Preparations, in II REMINGTON: THE
`SCIENCE AND PRACTICE OF PHARMACY, 19th ed., Ch. 89, 1563–76 (Alfonso
`R. Gennaro ed., 1995) (Ex. 1025, “Hecht”).
`
`9
`
`Samsung Bioepis Exhibit 1004
`Page 9
`
`

`

`A.
`
`IPR2022-01524
`Patent 11,253,572 B2
`
`supra Section I.B (Related Matters). In the absence of evidence to the
`contrary, we also find Dr. Del Priore to be competent to testify on the
`subject matter of his declaration, which is related to the subject matter of this
`proceeding. See Ex. 2021 ¶¶ 3–10, 16–18; see also infra Section II.A
`(identifying the parties’ proposed definition of the ordinarily skilled artisan,
`which is the same as that addressed by Dr. Del Priore).
`II. DISCUSSION
`LEVEL OF ORDINARY SKILL IN THE ART
`In determining the level of ordinary skill in the art, we consider the
`types of problems encountered in the art, the prior art solutions to those
`problems, the rapidity with which innovations are made, the sophistication
`of the technology, and the educational level of active workers in the field.
`Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962
`(Fed. Cir. 1986).
`Petitioner states,
`A POSA here would have: (1) knowledge regarding the
`diagnosis and treatment of angiogenic eye disorders, including
`the administration of 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),
`
`10
`
`Samsung Bioepis Exhibit 1004
`Page 10
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`including through the use of VEGF antagonists, or (ii) treating
`of same, including through the use of VEGF antagonists.
`Pet. 23 (citing Ex. 1002 ¶ 16). 9 Patent Owner neither contests this proposed
`definition of the ordinarily skilled artisan nor offers its own. See generally
`Prelim. Resp.
`For the purposes of this decision, we accept Petitioner’s proposed
`definition of the person of ordinary skill in the art (or ordinarily skilled
`artisan), which appears to be consistent with the level of skill in the art
`reflected in the prior art of record and the disclosure of the ’572 patent. See
`Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (“the prior art
`itself [may] reflect[]” evidence of the ordinary level of skill in the art)
`(quoting Litton Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158,
`163 (Fed. Cir. 1985)).
`B. CLAIM CONSTRUCTION
`The Board interprets claim terms in an inter partes review using the
`same claim construction standard that is used to construe claims in a civil
`action in federal district court. 37 C.F.R. § 42.100(b). In construing claims,
`district courts and the Board here, by default, give claim terms their ordinary
`and customary meaning, which is “the meaning that the term would have to
`a person of ordinary skill in the art in question at the time of the invention.”
`Phillips v. AWH Corp., 415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc).
`Should claim terms require express construction, sources for claim
`interpretation include “the words of the claims themselves, the remainder of
`the specification, the prosecution history [i.e., the intrinsic evidence], and
`extrinsic evidence concerning relevant scientific principles, the meaning of
`
`
`9 Petitioner uses “POSA” to refer to the person of ordinary skill in the art.
`
`11
`
`Samsung Bioepis Exhibit 1004
`Page 11
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`technical terms, and the state of the art.” Id. at 1314 (quoting Innova/Pure
`Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1116 (Fed.
`Cir. 2004)). “[T]he claims themselves [may] provide substantial guidance as
`to the meaning of particular claim terms.” Id. However, the claims “do not
`stand alone,” but are part of “‘a fully integrated written instrument’ . . .
`consisting principally of a specification that concludes with the claims,” and,
`therefore, the claims are “read in view of the specification.” Id. at 1315
`(quoting Markman v. Westview Instruments, Inc., 52 F.3d 967, 978–79 (Fed.
`Cir. 1995) (en banc)). Any special definition for a claim term must be set
`forth in the specification “with reasonable clarity, deliberateness, and
`precision.” In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). Without
`such a special definition, however, limitations may not be read from the
`specification into the claims. In re Van Geuns, 988 F.2d 1181, 1184 (Fed.
`Cir. 1993).
`“[W]e need only construe terms ‘that are in controversy, and only to
`the extent necessary to resolve the controversy.’” Nidec Motor Corp. v.
`Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017)
`(quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803
`(Fed. Cir. 1999)).
`We now turn to the parties’ positions on claim construction.
`“initial dose,” “secondary doses,” and “tertiary doses”
`1.
`One or all of the terms “initial dose,” “secondary doses,” and “tertiary
`doses,” appear in claims 1, 4, 9, 15, 16, 20, 24–27, and 29 (as noted, not all
`of these claims are challenged). See Ex. 1001, 23:1–25:5 (claims).
`
`12
`
`Samsung Bioepis Exhibit 1004
`Page 12
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`Petitioner asserts that the ’572 patent expressly defines the claim
`terms “initial dose,” “secondary doses,” and “tertiary doses,” in its
`Specification, as follows:
`The terms “initial dose,” “secondary doses,” and “tertiary
`doses,” refer to the temporal sequence of administration of the
`VEGF antagonist. Thus, the “initial dose” is the dose which is
`administered at the beginning of the treatment regimen (also
`referred to as the “baseline dose”); the “secondary doses” are
`the doses which are administered after the initial dose; and the
`“tertiary doses” are the doses which are administered after the
`secondary doses. The initial, secondary, and tertiary doses may
`all contain the same amount of VEGF antagonist, but will
`generally differ from one another in terms of frequency of
`administration. In certain embodiments, however, the amount
`of VEGF antagonist contained in the initial, secondary and/or
`tertiary doses will vary from one another (e.g., adjusted up or
`down as appropriate) during the course of treatment.
`Pet. 16 (quoting Ex. 1001, 3:51–65; citing Ex. 1002 ¶ 62).
`Patent Owner “does not propose a construction of ‘initial dose,’
`‘secondary dose[s],’ or ‘tertiary dose[s]’ that is different than that proposed
`by Petitioner,” although it also does not concede Petitioner’s proposal is
`correct. Prelim. Resp. 18.
`“When the specification explains and defines a term used in the
`claims, without ambiguity or incompleteness, there is no need to search
`further for the meaning of the term.” Multiform Dessicants Inc. v. Medzam
`Ltd., 133 F.3d 1473, 1478 (Fed. Cir. 1998). We agree with Petitioner’s
`unopposed position that the Specification of the ’572 patent expressly and
`unequivocally defines the claim terms “initial dose,” “secondary doses,” and
`“tertiary doses,” as set forth in the quote above, as meaning, respectively,
`(1) the dose which is administered at the beginning of the treatment
`regimen; (2) the doses administered after the initial dose; and (3) the doses
`
`13
`
`Samsung Bioepis Exhibit 1004
`Page 13
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`administered after the secondary doses. We interpret these terms consistent
`with the Specification’s definitions.
`“4 weeks” and “8 weeks” after the immediately preceding dose
`2.
`Petitioner contends that “[a] skilled artisan would understand the
`phrase “‘4 weeks’—as it appears in the Challenged Claims—to be
`synonymous with monthly administration” and “‘8 weeks’ . . . to be
`synonymous with bi- monthly (or every-other-month administration).”
`Pet. 17 (citing Ex. 1001, 8:9–11, 15:19–30; Ex. 1002 ¶¶ 65–66). Patent
`Owner does not challenge this construction. Prelim. Resp. 18.
`We determine that express construction of these claim terms is
`unnecessary for purposes of rendering this Decision. See Nidec Motor
`Corp., 868 F.3d at 1017.
`“wherein the patient achieves/gains”
`3.
`Claim 1 recites as its concluding clause, “wherein the patient achieves
`a gain in visual acuity within 52 weeks following the initial dose.” Ex. 1001,
`23:13–14 (italics added). Claims 2–4 and 8–10 further define this “gain in
`visual acuity.” Id. at 23:15–25, 23:32–38. Independent claim 15 and its
`dependent claims 16–26 are not challenged in this proceeding, and, although
`claim 15 has no gain in visual acuity requirement, claims 16–23 do. Id. at
`23:53–24:21. Independent claim 26 recites as its concluding clause,
`“wherein the method is as effective in achieving a gain in visual acuity as
`monthly administration of 0.5 mg of ranibizumab by intravitreal injection in
`human subjects with age-related macular degeneration at 52 weeks
`following the initial dose,” and dependent claim 28 further defines this “gain
`in visual acuity.” Id. at 24:40–44, 24:47–49 (italics added). Finally,
`independent claim 29 recites as its concluding clause, “wherein the method
`
`14
`
`Samsung Bioepis Exhibit 1004
`Page 14
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`is as effective in maintaining visual acuity as monthly administration of 0.5
`mg of ranibizumab by intravitreal injection in human subjects with age-
`related macular degeneration at 52 weeks following the initial dose,” and
`dependent claim 30 further defines this “gain in visual acuity.” Id. at 24:63–
`25:5 (italics added). Collectively we refer to these clauses, particularly of
`independent claims 1, 26, and 29, as the “results limitations.”
`Petitioner asserts that the results limitations merely state the intended
`results of the otherwise claimed methods of administering aflibercept and, as
`such, have no patentable weight because they do not alter the steps of the
`methods. Pet. 17. Petitioner’s position is that the results limitations should
`not be treated as limitations. Id. 17–20 (citing Ex. 1002 ¶ 67; Syntex
`(U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1378 (Fed. Cir. 2005); Bristol-
`Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1376 (Fed. Cir.
`2001); In re Copaxone, 2016 WL 873062, at *2 n.1–2 (D. Del. Mar. 7,
`2016); Endo Pharm. Inc. v. Watson Labs., Inc., 2014 WL 2859349, at *6, *8
`(E.D. Tex. Jun. 23, 2014)). Petitioner, however, accounts for the possibility
`that we find its position incorrect and alternatively argues under Grounds 1–
`4 that, if the results limitations are given patentable weight, then the asserted
`prior art inherently anticipated these limitations. See, e.g., id. at 38–39, 44–
`45 (citing Ex. 1002 ¶ 148; In re Montgomery, 677 F.3d 1375, 1382 (Fed.
`Cir. 2012)).
`Patent Owner argues that the results limitations require that the
`claimed patients and methods achieve particular “endpoints as assessed by
`the physician,” and that the results limitations are “‘condition[s] material to
`patentability,’ and therefore ‘cannot be ignored.’” Prelim. Resp. 18–19
`(citing Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329 (Fed. Cir. 2005)).
`
`15
`
`Samsung Bioepis Exhibit 1004
`Page 15
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`Patent Owner argues that “[t]he Visual Acuity [i.e., results] limitations in the
`Challenged Claims add additional requirements that may be—but are not
`necessarily—met upon performance of the dosing steps recited earlier in the
`claim,” and adds that the results limitations requirements are “not met unless
`the patient receiving the doses does, in fact, experience the required gain.”
`Id. at 20, 25 (italics added).
`The facts here are similar to those of Los Angeles Biomedical
`Research Institute at Harbor-UCLA Medical Center v. Eli Lilly & Co., 849
`F.3d 1049 (Fed. Cir. 2017) (“Los Angeles Biomed.”), where claims covered
`administering a pharmaceutical according to a certain regimen, to a person
`in need of treatment, and included a limitation in the body of the
`independent claim to a treatment result of “arresting or regressing” a tissue
`fibrosis by the administration of the recited dosage. Id. at 1053–54.
`Similarly here, as can be seen from claim 1 reproduced above at Section I.C
`(and each challenged independent claim), the claims are similarly directed to
`administering a pharmaceutical (aflibercept) to patients in need thereof, at a
`specified regimen and dosage, where a result of that treatment is expressly
`recited in the body of the independent claims. See Ex. 1001, 23:2–14 (claim
`1), 24:26–43 (claim 26), 24:50–67 (claim 29).
`In Los Angeles Biomed, in an inter partes review the Board construed
`the “arresting or regressing” clause to have no limiting role and to merely
`state an intended result, ultimately finding the claims unpatentable as
`obvious. Id. at 1054–57. The Federal Circuit disagreed and the Board’s
`decision was vacated and the case was remanded on, inter alia, that issue.
`Id. at 1067–68.
`
`16
`
`Samsung Bioepis Exhibit 1004
`Page 16
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`Relating to the claim construction, the Federal Circuit found that
`patent at issue was “clear” that the tissue fibrosis, recited by the claim as
`arrested or regressed by the otherwise recited treatment, was not the same as
`and did not necessarily accompany the symptom of erectile disfunction
`(taught in and the focus of the relied-upon prior art), although the former
`(fibrosis) may frequently result in the latter (disfunction). Id. at 1059. The
`Federal Circuit held that the “arresting or regressing” clause was more than a
`mere statement of intended result, but was a limitation carrying patentable
`weight because the phrase was drafted as a part of a separate step of the
`method rather than of the preamble, the “arresting or regressing” language
`demanded efficacy, and the efficacy was linked to specific treatment
`minimum duration and dosage. Id. at 1060–61. The patients exhibiting
`these two issues were not necessarily the same.
`In part because the Board did not consider the arresting/regressing
`result limitation in its unpatentability analysis, the Federal Circuit agreed
`with the patent owner that the Board’s findings were insufficient. Id. at
`1064, 1067. The Federal Circuit found that that prior art reference relied
`upon in the Board’s decision for teaching the claimed treatment, and also
`relied upon to link the condition of fibrosis with the symptom of erectile
`dysfunction, did not teach treating a population of patients suffering from
`erectile dysfunction only because of a fibrosis condition and, even though
`such patients may have had fibrosis, it was not certain; and further found
`that other cited prior art did not make certain a link between fibrosis and
`such dysfunction. Id. at 1065–66. This, the Federal Circuit found, was
`error.
`
`17
`
`Samsung Bioepis Exhibit 1004
`Page 17
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`We find in agreement with Patent Owner that the results limitations of
`the challenged claims are limitations and must be given patentable weight
`for the same reasons arresting or regressing a tissue fibrosis was a
`limitation in Los Angeles Biomed.
`Similarly, here the claims are directed to expressly required results of
`the administration of aflibercept to patients at 2 mg at an initial dose, in at
`least one secondary dose 4 weeks later, and in at least one tertiary dose 8
`weeks later. Therefore, we find that in claim 1, “wherein the patient
`achieves a gain in visual acuity within 52 weeks following the initial dose,”
`is a limitation. Further, in claim 26, “wherein the method is as effective in
`achieving a gain in visual acuity as monthly administration of 0.5 mg of
`ranibizumab by intravitreal injection in human subjects with age-related
`macular degeneration at 52 weeks following the initial dose,” is a limitation.
`And, in claim 29, “wherein the method is as effective in maintaining visual
`acuity as monthly administration of 0.5 mg of ranibizumab by intravitreal
`injection in human subjects with age-related macular degeneration at 52
`weeks following the initial dose,” is a limitation.
`“wherein exclusion criteria for the patient include both of . . .”
`4.
`Claim 14, which depends from claim 1, recites “exclusion criteria for
`the patient include both of: (1) active ocular inflammation; and (2) active
`ocular or periocular infection.” Ex. 1001, 23:49–53.
`Petitioner asserts that this recited subject matter should be entitled to
`no patentable weight under the printed matter doctrine because it is directed
`only to a mental step on the basis of information, i.e., deciding whether to
`treat a patient based on an instruction, with no functional relationship to the
`rest of the claimed method. Pet. 20–23.
`
`18
`
`Samsung Bioepis Exhibit 1004
`Page 18
`
`

`

`IPR2022-01524
`Patent 11,253,572 B2
`
`
`Patent Owner argues that the printed matter doctrine does not apply
`and the exclusion criteria should be given patentable weight because it
`defines the scope of patients to be treated and requires an assessment by the
`clinician. Prelim. Resp. 28–30.
`We determine that express construction of this claim term is
`unnecessary for purposes of rendering this Decision. See Nidec Motor
`Corp., 868 F.3d at 1017.
`C. APPLICABLE LEGAL STANDARDS
`“In an IPR, 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 (Fed. Cir. 2016) (citing 35 U.S.C.
`§ 312(a)(3) (requiring inter partes review petitions to identify “with
`particularity . . . the evidence that supports the grounds for the challenge to
`each claim”)). This burden of