Filed on behalf of: Celltrion, Inc.
`By: Lora M. Green (lgreen@wsgr.com)
`
`Yahn-Lin Chu (ychu@wsgr.com)
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________________
`
`
`CELLTRION, INC.,
`Petitioner,
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`
`_____________________________
`
`Case No. IPR2022-00257
`Patent No. 9,669,069
`
`_____________________________
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,669,069
`
`
`
`

`

`
`
`
`
`TABLE OF CONTENTS
`
`Page
`
`Introduction ...................................................................................................... 1 
`I. 
`Overview .......................................................................................................... 1 
`II. 
`III.  Mandatory Notices under 37 C.F.R. § 42.8 ..................................................... 4 
`A. 
`Real-Parties-in-Interest (37 C.F.R. § 42.8(b)(1)) .................................. 4 
`B. 
`Related Matters (37 C.F.R. § 42.8(b)(2)) .............................................. 4 
`C. 
`Lead and Back-Up Counsel and Service Information (37 C.F.R.
`§ 42.8(b)(3), (4)) .................................................................................... 5 
`IV.  Payment of Fees Under 37 C.F.R. § 42.15(a) and § 42.103 ........................... 6 
`V.  Grounds for Standing (37 C.F.R. § 42.104(a)) ................................................ 6 
`VI.  Threshold Requirement for Inter Partes Review ............................................ 7 
`VII.  Overview of Challenge and Precise Relief Requested .................................... 7 
`A. 
`Challenged Claims ................................................................................ 7 
`B. 
`Statutory Grounds of Challenge ............................................................ 7 
`VIII.  Overview of the ’069 Patent and Prosecution History .................................... 8 
`A. 
`The ’069 Patent ..................................................................................... 8 
`B. 
`Prosecution History ............................................................................. 11 
`IX.  Claim Construction ........................................................................................ 13 
`A. 
`“Initial Dose,” “Secondary Dose,” and “Tertiary Dose” .................... 14 
`1. 
`Regeneron’s contradictory construction for “tertiary
`dose,” if presented here, must be rejected. ............................... 15 
`“4 Weeks” and “Pro Re Nata (PRN)” ................................................. 18 
`“VEGFR1 Component,” “VEGFR2 Component,” and the
`“Multimerization Component.” ........................................................... 19 
`“Treating” ............................................................................................ 20 
`1. 
`The “method for treating” element of the preamble is not
`a limitation on the Challenged Claims, and therefore,
`does not require construction .................................................... 20 
`
`B. 
`C. 
`
`D. 
`
`-i-
`
`

`

`2. 
`
`3. 
`
`
`
`Regeneron’s anticipated argument that the “method for
`treating” preamble is a positive limitation should be
`rejected ...................................................................................... 22 
`If construed to be a limitation, the preamble’s plain and
`ordinary meaning—which does not provide any specific
`efficacy requirement—must govern ......................................... 23 
`Person of Ordinary Skill in the Art ................................................................ 25 
`X. 
`XI.  The Scope and Content of the Prior Art ........................................................ 26 
`A.  VEGF Trap-Eye/aflibercept Background ........................................... 26 
`B. 
`Petitioner’s Prior Art References ........................................................ 29 
`1. 
`Dixon (EX1006) ........................................................................ 31 
`2. 
`Regeneron (28-April-2008) (EX1012) ..................................... 33 
`3. 
`Heier-2009 (EX1020) ............................................................... 35 
`4. 
`Regeneron (30-April-2009) (EX1028) ..................................... 36 
`5. 
`The ’758 patent (EX1010) ........................................................ 37 
`6. 
`Dix (EX1033) ............................................................................ 37 
`7.  Mitchell (EX1030) .................................................................... 38 
`8. 
`Lalwani (EX1035) ..................................................................... 40 
`XII.  Grounds for Unpatentability – Detailed Analysis ......................................... 41 
`A.  Anticipation and Obviousness ............................................................. 41 
`1. 
`Legal Standards ......................................................................... 41 
`2. 
`Grounds 1 & 2: Claims 1 and 9-12 are anticipated by
`both Heier-2009 and Dixon, respectively ................................. 45 
`Ground 3: Regeneron (30-April-2009) anticipates claims
`1 and 9-12 .................................................................................. 49 
`Ground 4: VIEW1/VIEW2 disclosures in Dixon
`anticipate and/or render obvious claims 1 and 8-12 ................. 52 
`a. 
`Anticipation .................................................................... 53 
`b. 
`Obviousness .................................................................... 56 
`
`3. 
`
`4. 
`
`-ii-
`
`

`

`5. 
`
`
`
`b. 
`c. 
`d. 
`e. 
`f. 
`g. 
`
`Ground 5: The Challenged Claims are obvious over
`Heier-2009 in combination with either Mitchell or
`Dixon—and, optionally, either the ’758 patent or Dix ............. 59 
`a. 
`A skilled artisan would have been motivated to
`combine Heier-2009 with either Mitchell or Dixon ....... 61 
`Independent Claim 1 ....................................................... 61 
`Claim 8 ............................................................................ 64 
`Claims 9 and 10 .............................................................. 65 
`Claim 11 .......................................................................... 65 
`Claim 12 .......................................................................... 66 
`A skilled artisan would have reasonably expected
`success ............................................................................ 66 
`No Secondary Considerations ................................................... 68 
`6. 
`XIII.  Conclusion ..................................................................................................... 72 
`XIV.  Certificate of Compliance .............................................................................. 73 
`XV.  Appendix – List of Exhibits ........................................................................... 74 
`
`
`
`-iii-
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`

`

`
`
`I.
`
`INTRODUCTION
`
`Celltrion, Inc. (“Petitioner”) petitions for inter partes review (“IPR”) under
`
`35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42 et seq., seeking cancellation of claims 1
`
`and 8-12 (the “Challenged Claims”) of U.S. Patent No. 9,669,069 (“’069 patent,”
`
`EX1001), currently assigned to Regeneron Pharmaceuticals, Inc. (“Regeneron” or
`
`“Patent Owner”).
`
`II. OVERVIEW
`
`The Challenged Claims are drawn to nothing more than a known, mental step
`
`dosing regimen (i.e., “as-needed” or “pro re nata” (“PRN”) administration) using a
`
`drug known to persons of ordinary skill in the art (referred to herein as a “skilled
`
`artisan(s)”) to treat angiogenic eye disorders. These claims should have never
`
`issued. Each is anticipated and obvious over the prior art, which expressly disclosed
`
`skilled artisans actively practicing these exact methods on patients—with success.
`
`Indeed, Regeneron’s own clinical trials for EYLEA® (aka “VEGF Trap-Eye” or
`
`“aflibercept”)—widely published—utilized the claimed PRN dosing regimen to
`
`treat age-related macular degeneration (“AMD”) years before Regeneron filed the
`
`’069 patent application in 2011. Regeneron withheld those publications from the
`
`Examiner, allowing the ’069 patent to issue.
`
`By 2010, ophthalmologists were moving away from monthly dosing regimens
`
`for vitreoretinal disease therapies due to problems with patient compliance and
`
`-1-
`
`

`

`
`
`discomfort associated with intravitreal injections. For example, in 2007,
`
`LUCENTIS® (ranibizumab), an anti-VEGF therapy approved for monthly dosing,1
`
`was undergoing a series of clinical trials to assess less frequent dosing regimens.
`
`These clinical assessments included, inter alia, PRN dosing (including, PRN after
`
`three monthly loading doses). Motivated to keep pace with the LUCENTIS® trials,
`
`Regeneron initiated a clinical program for EYLEA® that implemented those same
`
`regimens—e.g., Regeneron’s Phase 2 clinical trials for age-related macular
`
`degeneration (“CLEAR-IT-2”) assessing PRN dosing after four monthly doses. The
`
`problem: this trial regimen was widely launched, published and thus known to
`
`skilled artisans long before 2011. The prior art includes numerous Regeneron press
`
`releases, which were directed to skilled artisans to attract their interest in EYLEA®,
`
`along with publications directed to practicing ophthalmologists. Many disclosed the
`
`CLEAR-IT-2 trial details, including, most notably, the later-claimed PRN dosing
`
`regimen. Those public disclosures render the Challenged Claims unpatentable.
`
`Petitioner files this Petition and supporting expert declarations from: (i)
`
`renowned ophthalmologist, Dr. Thomas Albini (EX1002), to apprise the Board of
`
`invalidating prior art—much of which was not before the Examiner when
`
`prosecuting the ’069 patent; and (ii) Dr. Mary Gerritsen, a pharmacologist with
`
`
`1 LUCENTIS® is the primary competitor to EYLEA®.
`
`-2-
`
`

`

`
`
`over thirty years’ experience, (EX1003) to confirm the public availability of certain
`
`prior art disclosures relied upon herein.
`
`Anticipation. Challenged Claims 1 and 9-12 are anticipated by three separate
`
`prior art references: Dixon, Heier-2009, and Regeneron (30-April-2009). Dixon
`
`and Heier-2009 disclose Regeneron’s Phase 2 CLEAR-IT-2 trial. Regeneron (30-
`
`April-2009) discloses Regeneron’s Phase 3 RVO trial regimen.
`
`Further, claims 1 and 8-12 are anticipated by Dixon in light of arguments that
`
`Regeneron itself made during prosecution of the ’069 patent. Dixon discloses
`
`Regeneron’s Phase 3 AMD (VIEW1/VIEW2) trial, which evaluated every-eight-
`
`week dosing (following a fixed monthly loading dose period)—a regimen
`
`Regeneron told the Examiner fell within the scope of the Challenged Claims.
`
`Obviousness. The Challenged Claims would also have been obvious. The
`
`prior art demonstrates—and Dr. Albini confirms—monthly intravitreal injections for
`
`angiogenic eye disorders were known to be burdensome—both physically and
`
`financially. Skilled artisans were thus moving away from monthly dosing VEGF
`
`antagonists in favor of less frequent schedules. For example, Genentech—following
`
`the industry trend—had showed success with PRN dosing (after three fixed monthly
`
`injections) for LUCENTIS®. Accordingly, a skilled artisan would have (1) been
`
`highly motivated to combine such knowledge with the prior art disclosures that
`
`-3-
`
`

`

`
`
`VEGF Trap-Eye is a potent, high-affinity VEGF blocker2, and (ii) reasonably
`
`expected success with the PRN dosing regimen based on the results from CLEAR-
`
`IT-2. In fact, although unnecessary to prove obviousness, the prior art
`
`demonstrates actual success, further confirming that the Challenged Claims are
`
`invalid and the claimed dosing regimen unpatentable.
`
`For the reasons set forth herein, Petitioner requests the Challenged Claims be
`
`cancelled.
`
`III. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`
`Pursuant to 37 C.F.R. §§ 42.8(a)(1) and 42.8(b), the following mandatory
`
`notices are provided as part of this Petition.
`
`A. Real-Parties-in-Interest (37 C.F.R. § 42.8(b)(1))
`
`Petitioner identifies the following real parties-in-interest: Celltrion, Inc.;
`
`Celltrion Healthcare Co. Ltd.; and Celltrion Healthcare U.S.A., Inc.
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`
`The ’069 patent is currently being challenged in Mylan Pharms. Inc. v.
`
`Regeneron Pharms., Inc., IPR2021-00880 (P.T.A.B.), instituted on November 10,
`
`
`2 EX1004, Holash; EX1005, Nguyen-2009; EX1006, Dixon; EX1007, Adis;
`
`EX1008, ’173 patent; EX1009, ’664 patent; see also EX1010, ’758 patent
`
`(disclosing nucleotide and amino acid sequences for aflibercept).
`
`-4-
`
`

`

`
`
`2021. This petition is concurrently filed with Celltrion, Inc. v. Regeneron Pharms.,
`
`Inc., IPR2021-00258 (P.T.A.B.), challenging U.S. Patent No. 9,254,338 (“’338
`
`patent”). The ’338 patent is currently being challenged in Mylan Pharms. Inc. v.
`
`Regeneron Pharms., Inc., IPR2021-00881 (P.T.A.B.), instituted on November 10,
`
`2021. To the best of Petitioner’s knowledge, there are no other judicial or
`
`administrative matters that would affect, or be affected by, a decision in this
`
`proceeding; nonetheless, out of an abundance of caution, Petitioner further
`
`identifies Chengdu Kanghong Biotechnology Co. v. Regeneron Pharms., Inc., Case
`
`No. PGR2021-00035 (P.T.A.B.).
`
`U.S. Patent Nos. 10,130,681 B2, 10,857,205 B2, 10,828,345 B2, and
`
`10,888,601 B2; and U.S. Patent Application Nos. 17/072,417, 17/112,063, and
`
`17/112,404 claim the benefit of the ’069 patent filing date.
`
`C. Lead and Back-Up Counsel and Service Information (37 C.F.R. §
`42.8(b)(3), (4))
`
`Lead Counsel:
`
`Lora M. Green (Reg. No. 43,541)
`
`Back-Up Counsel: Yahn-Lin Chu (Reg. No. 75,946)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Robert Cerwinski (to be admitted pro hac vice)
`
`Aviv Zalcenstein (to be admitted pro hac vice)
`
`Brigid Morris (to be admitted pro hac vice)
`
`
`
`-5-
`
`

`

`
`
`Petitioner hereby consents to electronic service. Please direct all
`
`correspondence to lead and back-up counsel at the contact information below. A
`
`power of attorney accompanies this petition.
`
`Email: lgreen@wsgr.com; ychu@wsgr.com; rcerwinski@geminilaw.com;
`
`azalcenstein@geminilaw.com; bmorris@geminilaw.com.
`
`Post: WILSON SONSINI GOODRICH & ROSATI, 1700 K Street NW
`
`5th Floor Washington, DC 20006
`
`Tel.: 202-791-8012
`
`IV. PAYMENT OF FEES UNDER 37 C.F.R. § 42.15(A) AND § 42.103
`
`The required fees are submitted herewith. If any additional fees are due at
`
`any time during this proceeding, the Office is authorized to charge such fees to
`
`Deposit Account No. 23-2415.
`
`V. GROUNDS FOR STANDING (37 C.F.R. § 42.104(A))
`
`Petitioner certifies that the ’069 patent—which issued on June 6, 2017—is
`
`available for IPR and that Petitioner is not barred or estopped from requesting an
`
`IPR challenging any claim of the ’069 patent on the grounds identified herein.
`
`Neither Petitioner nor any other real-party-in-interest has filed a civil action
`
`challenging the validity, or been served with a complaint alleging infringement
`
`of the ’069 patent, more than one year prior to this Petition’s filing. See
`
`-6-
`
`

`

`
`
`Motorola Mobility LLC v. Arnouse, No. IPR2013-00010, 2013 WL 12349001,
`
`*3 (P.T.A.B. Jan. 30, 2013).
`
`VI. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`This Petition meets and exceeds the threshold required under 35 U.S.C.
`
`§ 314(a). As explained below, for each ground, there is a reasonable likelihood that
`
`Petitioner will prevail with respect to at least one of the Challenged Claims.
`
`VII. OVERVIEW OF CHALLENGE AND PRECISE RELIEF REQUESTED
`A. Challenged Claims
`
`Petitioner requests IPR of claims 1 and 8-12 of the ’069 patent, and
`
`cancellation of these claims as unpatentable.
`
`B.
`
`Statutory Grounds of Challenge
`
`Each of the following prior art references and/or combinations of references
`
`renders the Challenged Claims invalid:
`
`Ground
`
`35 U.S.C.
`
`References
`
`CLEAR-IT-2, as disclosed in either
`
`1, 2
`
`§ 102
`
`Heier-2009 or Dixon
`
`3
`
`§ 102
`
`Regeneron (30-April-2009)
`
`Claims
`
`1, 9-12
`
`1, 9-12
`
`-7-
`
`

`

`4
`
`5
`
`
`
`§ 102
`
`and/or
`
`§ 103
`
`VIEW1/VIEW2, as disclosed in Dixon
`
`Heier-2009, in view of Mitchell or
`
`§ 103
`
`Dixon, and optionally, the ’758 patent
`
`or Dix
`
`
`
`
`
`1, 8-12
`
`
`
`1, 8-12
`
`Petitioner’s full statement of the reasons for the relief requested is set forth in
`
`greater detail below, and in the supporting declarations of Drs. Albini and
`
`Gerritsen.
`
`VIII. OVERVIEW OF THE ’069 PATENT AND PROSECUTION HISTORY
`A. The ’069 Patent3
`
`The ’069 patent claims a known dosing regimen for treating angiogenic eye
`
`disorders—including AMD—that amounts to administering a single initial dose of
`
`
`3 Solely for purposes of this IPR, Petitioner assumes a January 13, 2011 priority
`
`date. However, Petitioner reserves all rights to challenge the extent to which
`
`Regeneron asserts application of pre-AIA standards of patentability. The ’069
`
`patent is subject to the AIA given the inclusion of new matter in the Continuation-
`
`In-Part Application No. 13/940,370, filed July 12, 2013.
`
`-8-
`
`

`

`
`
`a VEGF antagonist (VEGF Trap-Eye)4, followed by one or more “secondary
`
`doses” administered two to four weeks after the immediately preceding dose,
`
`followed by one or more “tertiary doses” administered on a PRN basis. The
`
`specification establishes that angiogenic eye disorders, such as AMD, diabetic
`
`macular edema (“DME”), and retinal vein occlusion (“RVO”), were known to be
`
`effectively treated through the inhibition of vascular endothelial growth factor
`
`(“VEGF”). EX1001, ’069 patent, 1:24-53.
`
`The specification also sets forth AMD dosing regimens employing PRN
`
`dosing disclosed in the prior art before the ’069 patent application was filed,
`
`including the Phase 2 monthly loading dose/PRN regimen and the Phase 3 loading
`
`dose/every-eight-week regimen, in which patients received PRN injections in the
`
`second year. Id., 8:19-49 (Example 2, disclosing CLEAR-IT-2); id., 9:11-13:49
`
`(Example 4).
`
`Example 2, like the prior art, lists the five treatment arms in the CLEAR-IT-
`
`2 trial, including administering VEGF Trap-Eye via intravitreal injection to AMD
`
`
`4 Vascular endothelial growth factor or VEGF is a “naturally occurring
`
`glycoprotein in the body that acts as a growth factor for endothelial cells.”
`
`EX1011, Semeraro, 711. Early research linked activity of VEGF-A to the
`
`development of ocular diseases such as neovascular AMD. Id.
`
`-9-
`
`

`

`
`
`patients at a fixed interval (e.g., four-week) for the first 12 weeks. Id., 8:26-33.
`
`After 12 weeks, subjects “were evaluated every 4 weeks for 9 months, during
`
`which additional doses were administered based on pre-specified criteria.” Id.,
`
`8:29-33. In other words, subjects assigned to the “4-week” fixed interval groups
`
`received four monthly doses, followed by PRN dosing.5
`
`Example 4 describes parallel Phase 3 clinical trials carried out to investigate
`
`the use of VEGF Trap-Eye to treat AMD: the VIEW1/VIEW2 trials.6 EX1001,
`
`’069 patent, 9:11-13:49. Example 4 discloses that patients enrolled in
`
`VIEW1/VIEW2 were assigned to one of four treatment arms employing varying
`
`dosing regimens for the first year of the study (id., 9:45-58); whereas the second
`
`year reverted to PRN dosing for all subjects (id., 9:63-10:13 (“During the second
`
`year of the study, subjects will be evaluated every 4 weeks and will receive
`
`[intravitreal] injection of study drug at intervals determined by specific dosing
`
`criteria.”)). Most notably, Arm-2Q8 involved “2 mg VEGFT administered every 4
`
`
`5 The CLEAR-IT-2 PRN dosing regimen was disclosed in the prior art by at
`
`least 2008. EX1012, Regeneron (28-April-2008), 1.
`
`6 The VIEW1/VIEW2 trials were fully disclosed in the prior art as early as
`
`2008. EX1013, Regeneron (8-May-2008), 1; EX1014, NCT-795, 8; EX1015,
`
`NCT-377, 6.
`
`-10-
`
`

`

`
`
`weeks to week 8 and then every 8 weeks.” (Id., 9:45-58). That is, VEGF Trap-Eye
`
`was administered in three monthly doses, followed by eight-week dosing intervals
`
`in the first year, followed by PRN dosing in the second year.
`
`B.
`
`Prosecution History
`
`During prosecution, Regeneron made several arguments against the
`
`Examiner’s rejections over Regeneron’s Monthly-Dosing Patents7 for obviousness-
`
`type-double-patenting (“OTDP”). First, Regeneron argued that its Monthly-Dosing
`
`Patents did not disclose the exact regimen of the PRN dosing claims. EX1017,
`
`’069 FH, 1/30/2017 Amendment, 5. Second, Regeneron represented that once-per-
`
`month dosing was the standard of care and alleged the less frequent administration
`
`under the Challenged Claims produced unexpected results. Id., 6-8.
`
`Third, and most notably, Regeneron presented the VIEW1/VIEW2 results—
`
`published in Heier-2012 (EX1018)—as purported evidence of surprising and
`
`unexpected results, in attempt to support the Challenged Claims’ patentability. (Id.,
`
`6-8). Specifically, Regeneron asserted:
`
`
`7 Regeneron’s “Monthly-Dosing Patents” refers to U.S. Patent Nos. 7,303,746;
`
`7,303,747; 7,306,799; and 7,521,049; which generally disclose doses separated by
`
`at least two weeks. See EX1016, Monthly-Dosing Patents.
`
`-11-
`
`

`

`
`
`[T]he results show that the treatment groups which were compared
`
`with the monthly treatment groups surprisingly did not obtain an
`
`inferior result. As such, the PRN treatment protocol as encompassed
`
`by the presently pending independent claim 1 achieves results which
`
`are as good or better than the results obtained with monthly treatment.
`
`Id. In other words, Regeneron told the Examiner that the VIEW1/VIEW2, every-
`
`eight-week dosing regimen represents a “PRN treatment protocol.” EX1017, ’069
`
`FH, 1/30/2017 Amendment, 6 (“Heier et al. paper shows results of a treatment
`
`protocol of the type claimed.”) (emphasis added).
`
`As purportedly further support, Regeneron stated that Heier-2012 echoes the
`
`’069 patent’s conclusion that administration “at a frequency of once every 8
`
`weeks, following a single initial dose and two secondary doses administered four
`
`weeks apart, resulted in significant prevention of moderate or severe vision loss or
`
`improvements in visual acuity.” Id., 7-8 (emphasis added); id., 8 (alleging “the
`
`claimed treatment protocol provides enormous advantages to patients” based on
`
`-12-
`
`

`

`
`
`outcomes observed in Heier-2012 for the every-two-month VIEW1/VIEW2 dosing
`
`regimen) (emphasis added).8
`
`Regeneron lastly argued that Example 5 “illustrates an administration
`
`regimen encompassed by [issued] claim 1 (i.e., 3 initial doses of VEGF Trap
`
`administered once every four weeks, followed by additional doses administered as
`
`needed (PRN)) for the effective treatment of diabetic macular edema.” Id., 7.
`
`IX. CLAIM CONSTRUCTION
`
`In accordance with 37 C.F.R. § 42.100(b), the Challenged Claims must be
`
`“construed using the same claim construction standard that would be used to
`
`construe the claim in a civil action under 35 U.S.C. § 282(b),” i.e., the Phillips
`
`standard. 83 Fed. Reg. 197, 51340-51359 (Oct. 11, 2018); Phillips v. AWH Corp.,
`
`415 F.3d 1303, 1312 (Fed. Cir. 2005). Here, Petitioner and expert declarant, Dr.
`
`Albini, have applied this standard.
`
`
`8 Regeneron never informed the Examiner that the VIEW dosing regimen in
`
`Heier-2012 was the subject of numerous pre-2011 public disclosures (discussed in
`
`greater detail below).
`
`-13-
`
`

`

`
`
`A.
`
`“Initial Dose,” “Secondary Dose,” and “Tertiary Dose”
`
`The Challenged Claims recite the phrases “initial dose,” “secondary dose,”
`
`and “tertiary dose.” A skilled artisan would understand each as expressly defined
`
`in the ’069 patent specification:
`
`
`
`EX1001, ’069 patent, 3:34-48 (emphasis added). The specification further explains
`
`that “the immediately preceding dose” means “in a sequence of multiple
`
`administrations, the dose of VEGF antagonist which is administered to a patient
`
`prior to the administration of the very next dose in the sequence with no
`
`intervening doses.” Id., 3:54-59; see also EX1002, Albini, ¶40. Petitioner proposes
`
`that each claim term be construed consistent with these express definitions: “initial
`
`dose” means “the dose which is administered at the beginning of the treatment
`
`regimen”; “secondary dose(s)” means “the dose(s) which are administered after the
`
`-14-
`
`

`

`
`
`initial dose”; and “tertiary dose(s)” means “the dose(s) which are administered
`
`after the secondary dose(s).”
`
`1.
`
`Regeneron’s contradictory construction for “tertiary dose,”
`if presented here, must be rejected.
`To the extent Regeneron proposes the same construction for “tertiary dose”
`
`that it has in the ’345 Patent PGR—i.e., “dose(s) that maintain(s) a therapeutic
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`effect throughout the course of treatment,” (PO Preliminary Response, Chengdu
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`Kanghong Biotechnology Co. v. Regeneron Pharms., Inc., No. PGR2021-00035,
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`Paper 6, 9 (P.T.A.B. Apr. 15, 2021) (“’345 Patent PGR”))—it should be rejected
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`for at least the following reasons.
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`First and foremost, as described above, the ’069 patent specification recites
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`an express definition that provides the patentees’ intended meaning to the claims:
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`
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`EX1001, ’069 patent, 3:40-41 (emphasis added). The term is “set off by quotation
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`marks,” which “[is] often a strong indication that what follows is a definition”—
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`“the patentee must be bound by the express definition.” Sinorgchem Co., Shandong
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`v. Int’l Trade Comm’n, 511 F.3d 1132, 1136 (Fed. Cir. 2007). In other words,
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`“tertiary dose” is “clearly, deliberately, and precisely defined,” (id.), in the ’069
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`patent—nothing more is needed and there is no basis for straying from that express
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`definition.
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`Second, Regeneron’s proposed construction is unsupported and the intrinsic
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`record does not suggest reading-in limitations. Phillips, 415 F.3d at 1323
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`(reaffirming the need “to avoid the danger of reading limitations from the
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`specification into the claim”). For example, Regeneron relies exclusively on
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`column 2 as purported support for its narrowed construction (’345 Patent PGR,
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`11), but that specification passage only describes a single embodiment—i.e.,
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`bimonthly dosing— and is not even relevant to the “as-needed/pro re nata (PRN)”
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`dosing regimen(s) of the Challenged Claims. EX1001, ’069 patent, 2:14-16
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`(“[E]ach tertiary dose is administered at least 8 weeks after the immediately
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`preceding dose.”) (emphasis added).9 By comparison, the express definition recited
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`9 The ’338 patent purportedly claims this dosing regimen, with bimonthly doses
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`as the “tertiary doses.” However, Regeneron’s proposed construction for “tertiary
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`doses” is in conflict with the language of the ’338 patent claims, which require
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`“tertiary doses” administered “at least 8 weeks after the immediately preceding
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`dose” irrespective of whether the injection “maintain[s] a therapeutic effect.” See
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`EX1019, ’338 patent, 23:2-18, id., 24:24-25 (claims 1 and 17). Consequently, the
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`’338 patent—which derives from the same parent application as the ’069 patent
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`and the Chengdu-challenged ’345 patent—would improperly require a different
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`construction of “tertiary dose” for those claims to have meaning, further
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`in the specification (i.e., “doses which are administered after the secondary doses”)
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`provides the exact temporal and sequential distinction from the other doses in the
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`regimen that the patent drafters intended. EX1001, ’069 patent, 3:34-36 (“The
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`terms … refer to the temporal sequence of administration.”). Merck & Co. v. Teva
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`Pharms. USA, Inc., 395 F.3d 1364, 1372 (Fed. Cir. 2005) (“A claim construction
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`that gives meaning to all the terms of the claim is preferred over one that does not
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`do so.”). No further construction is necessary. Multiform Desiccants, Inc. v.
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`Medzam, Ltd., 133 F.3d 1473, 1478 (Fed. Cir. 1998) (“When the specification
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`explains and defines a term used in the claims, without ambiguity or
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`incompleteness, there is no need to search further for the meaning of the term.”).
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`Third, Regeneron’s proposal improperly injects ambiguity and indefiniteness
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`where there is none. Ruckus Wireless, Inc. v. Innovative Wireless Sols., LLC, 824
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`F.3d 999, 1004 (Fed. Cir. 2016) (rejecting a construction encompassing subject
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`matter that would render the claims invalid under § 112). Regeneron’s proposed
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`illustrating the extent to which Regeneron’s proposed construction, if presented in
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`this IPR, would inject indefiniteness into the claims. Samsung Elecs. Co. v. Elm
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`3DS Innovations, LLC, 925 F.3d 1373, 1378 (Fed. Cir. 2019) (“Where multiple
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`patents derive from the same parent application and share many common terms, we
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`must interpret the claims consistently across all asserted patents.”).
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`construction, itself, requires construction—i.e., “maintain,” “therapeutic effect,”
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`and “throughout the course of treatment” lack definition and plain and ordinary
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`meanings. A skilled artisan is therefore left wondering what Regeneron’s
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`construction is supposed to mean, as well as what metrics one is supposed to use to
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`assess each imported limitation. Moreover, Regeneron’s added language renders
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`the “as-needed/pro re nata” element of the Challenged Claims—which a skilled
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`artisan would already understand as administration to maintain a therapeutic
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`benefit— duplicative and meaningless. Power Mosfet Techs., L.L.C. v. Siemens
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`AG, 378 F.3d 1396 (Fed. Cir. 2004) (“[I]nterpretations that render some portion of
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`the claim language superfluous are disfavored.”).
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`Finally, Regeneron notably ignores “initial” and “secondary.” Consequently,
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`a skilled artisan, under Regeneron’s proposal, is uncertain whether those terms
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`carry “therapeutic effect” limitations as well, or whether the specification’s express
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`definitions apply—adding further uncertainty and ambiguity to the Challenged
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`Claims. Petitioner’s proposal to apply the express definitions for all three terms, on
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`the other hand, is clear to a skilled artisan and free of the ambiguity of Regeneron’s
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`proposed construction.
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`B.
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`“4 Weeks” and “Pro Re Nata (PRN)”
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`“4 weeks.” Challenged claims 1, 2, and 8 recite the term “4 weeks.” A
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`skilled artisan would understand “4 weeks” as “monthly” administration. EX1001,
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`-18-
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`’069 patent, 7:58-59 (“‘[M]onthly’ dosing is equivalent to dosing once every four
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`weeks.”); id., 14:47-48 (patients received “monthly injections,” which “means
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`patients who received … injections once every four weeks”); EX1002, Albini, ¶41.
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`“Pro Re Nata (PRN).” Independent claim 1 recites the term “pro re nata
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`(PRN),” which is expressly defined in the claim language as “as-needed.” EX1001,
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`’069 patent, 21:50-51 (“administered on an as-needed/pro re nata (PRN) basis”).
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`The specification is consistent with the claim language and with the term’s use
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`among skilled artisans. EX1001, ’069 patent, 14:43 (“as-needed (PRN”), 15:43-48
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`(“administered pro re nata (PRN) based on visual and/or anatomical outcomes”),
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`16:9-49; EX1002, Albini, ¶43.
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`C.
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`“VEGFR1 Component,” “VEGFR2 Component,” and the
`“Multimerization Component.”
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`Claim 1 of the ’069 patent recites that the “VEGF antagonist” comprises a
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`“VEGFR1 component,” a “VEGFR2 component,” and a “multimerization
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`component.” According to the ’069 patent, these terms all refer to separate amino
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`acid domains of “SEQ ID NO:2.” A skilled artisan would understand these terms
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`to collectively refer to aflibercept (i.e., VEGF Trap, VEGF Trap-Eye, or
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`VEGFR1R2- FcΔC1(a)). EX1001, ’069 patent, 2:34-38; EX1002, Albini, ¶39.
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`D.
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`“Treating”
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`1.
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`The “method for treating” element of the preamble is not a
`limitation on the Challenged Claims, and therefore, does
`not require construction
`The “method for treating” element of independent claim 1 is “merely a
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`statement of purpose or intended use” for the claimed dosing regimen(s) and is
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`non-limiting. Bristol-Myers Squibb Co. v. Ben Venue Lab’ys, Inc., 246 F.3d 1368,
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`1375 (Fed. Cir. 2001); Vizio, Inc. v. Int’l Trade Comm’n, 605 F.3d 1330, 1340-41
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`(Fed. Cir. 2010); Arctic Cat Inc. v. GEP Power Prods., Inc., 919 F.3d 1320, 1327
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`(Fed. Cir. 2019) (“as a general rule preamble language is not treated as limiting”).
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`Indeed, “method for treating”—like the “method” preamble in Bio-Rad—neither
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`provides antecedent basis for any other claim element10 nor gives life, meaning or
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`vitality to the claimed dosing regimen, and thus, it is not a limitation. Bio-Rad
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`Lab’ys, Inc. v. 10X Genomics Inc., 967 F.3d 1353, 1371 (Fed. Cir. 2020) (citing
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`TomTom, Inc. v. Adolph, 790 F.3d 1315, 1322-25 (Fed. Cir. 2015)) (“In TomTom
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`… [t]he two-part preamble of the asserted claim recited: ‘[1] [a] method for
`
`generating an