e-dokumen.com

-2-studypatients?releaseid 445521 (“Regeneron (18-February-2010)”)1048Press Release, Bayer, Bayer HealthCare and Regeneron AnnounceVEGF Trap-Eye Achieved Durable Improvement in Vision Over 52Weeks in a Phase 2 Study in Patients with Age-Related MacularDegeneration (Aug. 19, 2008) (“Bayer (19-August-2008)”)1049Campochiaro et al., Antagonism of vascular endothelial growth factorfor macular edema caused by retinal vein occlusions: two-yearoutcomes, Ophthalmology, 117 (2010), pp. 2387-2394.(“Campochiaro”)1050Adam Hayes, SEC Filings: Forms You Need To Know, INVESTOPEDIA(Jan. 18, 2021), nalysis/08/sec-forms.asp (“Hayes”)1051Owen A. Anderson et al., Delivery of Anti-Angiogenic MolecularTherapies for Retinal Disease, 15 DRUG DISCOVERY TODAY 272(2010) (“Anderson”)1052Thomas A. Ciulla & Philip J. Rosenfeld, Antivascular EndothelialGrowth Factor Therapy For Neovascular Age-Related MacularDegeneration, 20 CURRENT OPINION OPHTHALMOLOGY 158 (2009)(“Ciulla”)1053Zhang Ni & Peng Hui, Emerging Pharmacologic Therapies for WetAge-Related Macular Degeneration, 223 OPHTHALMOLOGICA 401(2009) (“Ni”)1054Marco A. Zarbin & Philip J. Rosenfeld, Pathway-Based Therapies forAge-Related Macular Degeneration: An Integrated Survey ofEmerging Treatment Alternatives, 30 RETINA 1350 (2010) (“Zarbin”)1055Corporate Finance Institute, SEC Filings: Public Disclosures AboutPublic sources/data/public-filings/secfilings/ (last visited May 5, 2021) (“Corporate Finance Institute”)1056Carl W. Schneider, Nits, Grits, and Soft Information in SEC Filings,121 U. PA. L. REV. 254 (1972) (“Schneider”)ix

1057Justin Kuepper, The Best Investment Information Sources: Using SECFilings, Analyst Reports, and Company Websites, BALANCE (Jan. 13,2021), estorinformation-1979207 (“Kuepper”)1058Kristina Zucchi, EDGAR: Investors’ One-Stop-Shop For CompanyFilings, YAHOO!LIFE (Jan. 31, h/edgar-investors-onestop-shop-170000800.html (“Zucchi”)x

Apotex Inc. (“Petitioner”) petitions for inter partes review (“IPR”) under 35U.S.C. §§ 311–319 and 37 C.F.R. §§ 42 et seq., seeking cancellation of claims 1-14and 26-30 (the “Challenged Claims”) of U.S. Patent No. 11,253,572 (“‘572 patent”)(Ex.1001), assigned to Regeneron Pharmaceuticals, Inc. (“Regeneron” or “PatentOwner”).I.INTRODUCTIONThe Challenged Claims are directed to a method of treating a knownindication with a known dosage regimen of a known active ingredient. Long beforethe patent’s alleged 2011 priority date, Regeneron had disclosed that it’s age-relatedmacular degeneration (“AMD”) clinical trials (VIEW1/VIEW2) with EYLEA (aflibercept) were designed to use the precise dosing regimen now covered by theChallenged Claims. Regeneron publicly disclosed the exact dosing regimen as earlyas 2008, three years prior to filing its patent application. While Regeneron addedcertain efficacy endpoints that result upon administering the claimed dosageregimen, such claim elements are not given patentable weight. But even if theywere, the prior art nevertheless anticipates the Challenged Claims.The caselaw is clear here. It is not patentable to merely observe the efficacyof administering a known compound using a known method to treat a knowncondition. See, e.g., In re Montgomery, 677 F.3d 1375, 1381 (Fed. Cir. 2013); KingPharms., Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1275 (Fed. Cir. 2010); In re1

Omeprazole Patent Litig., 483 F.3d 1364, 1373 (Fed. Cir. 2007); Perricone v.Medicis Pharm. Corp., 432 F.3d 1368, 1378 (Fed. Cir. 2005); Bristol–Myers SquibbCo. v. Boehringer Ingelheim Corp., 86 F. Supp. 2d 433, 443 (D.N.J. 2000), aff'd inrelevant part, 246 F.3d 1368 (Fed. Cir. 2001). Simply put, the Challenged Claimsare not patentable.II.MANDATORY NOTICES (37 C.F.R. § 42.8)Pursuant to 37 C.F.R. §§ 42.8(a)(1) and 42.8(b), the following mandatorynotices are provided as part of this Petition.A.REAL PARTIES-IN-INTEREST (37 C.F.R. § 42.8(b)(1))Petitioner Apotex Inc. is the real party-in-interest. Additional real parties-ininterest are Apotex Corp., Apotex Pharmaceutical Holdings Inc. and AposhermDelaware Holdings Corp.No other parties exercised or could have exercised control over this Petition;no other parties funded, directed and controlled this Petition. See Trial PracticeGuide, 77 Fed. Reg. 48759- 60 (Aug. 14, 2021).B.RELATED MATTERS (37 C.F.R. § 42.8(b)(2))Petitioner identifies the following IPR proceedings that are currently pendingon patents related to the ’572 patent: Challenging U.S. Patent No. 9,254,338 (the ‘338 patent):2

o Mylan Pharms. Inc. v. Regeneron Pharms. Inc., No. IPR202100881 (P.T.A.B.), filed May 5, 2021,o Celltrion Inc. v. Regeneron Pharms, Inc., No. IPR2022-00258(P.T.A.B.), filed December 9, 2021, ando Apotex Inc. v. Regeneron Pharms, Inc., No. IPR2022-00298(P.T.A.B.), filed December 9, 2021. Challenging U.S. Patent No. 9,669,069:o Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No. IPR202100880 (P.T.A.B.), filed May 5, 2021,o Celltrion Inc. v. Regeneron Pharms, Inc., No. IPR2022-00257(P.T.A.B.), filed December 9, 2021, ando Apotex Inc. v. Regeneron Pharms, Inc., No. IPR2022-00301(P.T.A.B.), filed December 9, 2021. Challenging U.S. Patent No. 10,130,681:o Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No. IPR202201225 (P.T.A.B.), filed July 1, 2022. Challenging U.S. Patent No. 10,888,601:3

o Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No. IPR202201226 (P.T.A.B.), filed July 1, 2022.Petitioner identifies the following district court proceeding that is currentlypending and involves the ‘572 patent as well as related patents: Regeneron Pharms.,Inc. v. Mylan Pharms. Inc., No. 1:22-cv-00061-TSK (N.D. W.Va).To the best of Petitioner’s knowledge, there are no other judicial oradministrative matters that would affect, or be affected by, a decision in thisproceeding; nonetheless, out of an abundance of caution, Petitioner further identifiesChengdu Kanghong Biotechnology Co. v. Regeneron Pharms., Inc., No. PGR202100035 (P.T.A.B.).U.S. Patent Nos. 9,254,338; 9,669,069; 10,130,681; 10,857,205; 10,828,345;and 10,888,601; and U.S. Patent Application Nos. 17/072,417; 17/112,404;17/112,063; and 17/350,958 are all related to the ’572 patent.C.LEAD AND BACK-UP COUNSEL AND SERVICEINFORMATION (37 C.F.R. § 42.8(b)(3)-(4))Petitioner identifies its lead and backup counsel below. A Power of Attorneyis filed concurrently herewith under 37 C.F.R. § 42.10(b).LeadBack-UpTeresa Stanek Rea (Reg. No. 30,427)CROWELL & MORING LLPIntellectual Property GroupDeborah H. Yellin (Reg. No. 45,904)CROWELL & MORING LLPIntellectual Property Group4

1001 Pennsylvania Avenue, N.W.Washington, DC 20004-2595Telephone No.: (202) 624-2620Facsimile No.: (202) [email protected] Pennsylvania Avenue, N.W.Washington, DC 20004-2595Telephone No.: (202) 624-2947Facsimile No.: (202) [email protected] M. Lentz (Reg. No. 65,382)CROWELL & MORING LLPIntellectual Property Group1001 Pennsylvania Avenue, N.W.Washington, DC 20004-2595Telephone No.: (202) 624-2897Facsimile No.: (202) [email protected] direct all correspondence to lead and back-up counsel at the rvicebyemailat:[email protected], [email protected], and [email protected] UNDER 37 C.F.R. § 42.15(a) AND § 42.103The required fees are submitted herewith. The undersigned representative ofPetitioner hereby authorizes the Patent Office to charge any additional fees or creditany overpayment to Deposit Account No. 05-1323 (Customer ID No. 23911).IV.GROUNDS FOR STANDING (37 C.F.R. § 42.104(a))Petitioner certifies that the ‘572 patent—which issued on February 22, 2022—is available for IPR and that Petitioner is not barred or estopped from requesting anIPR challenging any claim thereof on the grounds identified herein. NeitherPetitioner nor any other real party-in-interest has filed a civil action challenging the5

validity, or been served with a complaint alleging infringement, of the ‘572 patent,more than one year prior to the filing of this Petition. See Motorola Mobility LLC v.Arnouse, No. IPR2013-00010, 2013 WL 12349001, *3 (P.T.A.B. Jan. 30, 2013).V.THE BOARD SHOULD NOT EXERCISE ITS DISCRETION TODENY INSTITUTIONThe Board should not exercise its discretion to deny institution based on themere citation by the Applicant of certain references used in this Petition inInformation Disclosure Statements (“IDS”). The examiner’s failure to address anyof the references used in this Petition on the merits favors institution.To apply §325(d), the Board uses the following two-part framework: “(1)whether the same or substantially the same art previously was presented to the Officeor whether the same or substantially the same arguments previously were presentedto the Office; and (2) if either condition of first part of the framework is satisfied,whether the petitioner has demonstrated that the Office erred in a manner materialto the patentability of the challenged claims.” Advanced Bionics, LLC v. Med-ElElektromedizinische Gerate GmbH, IPR2019-01469, Paper 6 at 8 (PTAB Feb. 13,2020). “An example of material error may include misapprehending or overlookingspecific teachings of the relevant prior art where those teachings impact patentabilityof the challenged claims.” Id. at 8 n.9. In applying this two-part framework, theBoard has identified several nonexclusive factors that may be considered (“the6

Becton factors”). Becton, Dickinson & Co. v. B. Braun Melsungen AG, IPR201701586, Paper 8 at 17-18 (PTAB Dec. 15, 2017). Factors (a), (b), and (d) correspondto the first part of the framework, and factors (c), (e), and (f) fall within part two ofthe framework. Advanced Bionics, at 8-10.Dixon, Regeneron (8-May-2008), NCT-795, and NCT-377, used in thisPetition as anticipatory references, are merely a few of the hundreds of referencessubmitted to the Patent Office in various Information Disclosure Statements duringthe very short prosecution. Although the examiner acknowledged the IDSs, there isno evidence that he substantively considered the references relied upon herein. Infact, the Examiner did not present any rejections based on prior art in the one andonly Office Action, instead only presenting double patenting rejections over severalpatents in the same family.The Board “has consistently declined exercising its discretion under Section325(d) when the only fact a Patent Owner can point to is that a reference wasdisclosed to the Examiner during the prosecution.” Amgen Inc. v. Alexion Pharm.,Inc., IPR2019-00740, Paper 15 at 65 (PTAB Aug. 30, 2019); Amneal Pharms. LLCv. Alkermes Pharma Ireland Ltd., IPR2018-00943, slip op. at 40 (PTAB Nov. 7,2018) (Paper 8) (declining to deny institution based on § 325(d) where reference waslisted on the face of the patent, but patent owner provided no evidence “about theextent to which the [e]xaminer evaluated” the reference during prosecution); Digital7

Check Corp. d/b/a ST Imaging v. E-Imagedata Corp., IPR2017-00178, slip op. at12-13 (PTAB Apr. 25, 2017) (Paper 6) (granting institution even though a prior artreference was cited in an IDS because there was no indication that the claims weresubstantively discussed by the examiner during prosecution); Fox Factory, Inc. v.SRAM, LLC, IPR2016-01876, slip op. at 7-9 (PTAB Apr. 3, 2017) (Paper 8)(refusing to deny institution based on § 325(d) when a prior art reference was citedin an IDS but was not considered by the examiner at any length). This pattern isparticularly consistent where, as here, a relevant reference is merely cited in an IDSbut not applied by the Examiner in making a rejection. See Apotex, Inc. v. UCBBiopharma, SPRL, IPR2019-00400, Paper 17 at 24-25 (PTAB July 15, 2019).Petitioner does not contend that Dixon, Regeneron (8-May-2008), NCT-795,and NCT-377 were not presented to the Office. Thus, the relevant analysis hererelates to part two of the Advanced Bionics framework. Part two of the AdvancedBionics framework considers whether the petitioner has demonstrated that the Officeerred in a manner material to the patentability of the challenged claims. AdvancedBionics, at 8. As Advanced Bionics explains, considering Becton factors (c), (e), and(f) can provide guidance as to whether the Office erred. Roku, Inc. v. UniversalElecs., Inc., IPR2019-01619, Paper 11 at 12 (PTAB Apr. 2, 2020). As explainedbelow, each of these factors demonstrate the material error by the Office.8

Regarding factor (c), there is no evidence that Dixon, Regeneron (8-May2008), NCT-795, or NCT-377 were evaluated at all during examination, and it isindisputable that they were never the basis for a rejection. There is no discussion ofany of these references in the one Office Action in the ’572 patent’s prosecutionhistory. This factor therefore weighs strongly against exercising § 325(d) discretion.See Hyperbranch Med. Tech., Inc. v. Confluent Surgical, Inc., IPR2018-01097,Paper 14 at 24 (PTAB Nov. 14, 2018) (Prior art “simply being of record, but notapplied in any rejection by the Examiner during examination , provides littleimpetus for [the Board] to exercise [its] discretion to deny institution under §325(d)”); Mylan Pharm. Inc. v. Merck Sharp & Dohme Corp., IPR2020-00040,Paper 21 at 18 (PTAB May 12, 2020) (finding material error where “[t]he Examinernever discussed [asserted prior art cited in IDS] or made a rejection based on it”).Regarding factors (e) and (f), as demonstrated herein, the asserted referencesanticipate all but four of the Challenged Claims, and these references, in combinationwith a reference that was not before the Office during prosecution (Hecht) rendersobvious the remaining Challenged Claims. Thus, Petitioner has demonstrated thatthe Examiner’s failure to consider Dixon, Regeneron (8-May-2008), NCT-795, orNCT-377 and the disclosures relied on in this Petition constitutes material error. TheAmgen case cited above is highly instructive in this regard. The Board held that thefailure of the examiner to apply prior art that served as the primary reference in an9

IPR can itself constitute material error. Amgen, IPR2019-00740, Paper 15 at 65.And, in arriving at that holding, the Board credited five other proceedings where theBoard declined to exercise its discretion under § 325(d) when a reference waspreviously disclosed, but never substantively considered by the Examiner. AmnealPharms., IPR2018-00943, Paper 8 at 40; Digital Check, IPR2017-00178, Paper 6 at12–13; Fox Factory, IPR2016-01876, Paper 8 at 7–9; HyperBranch Med. Tech.,IPR2018-01097, Paper 14 at 17; Praxair Distrib., Inc. v. INO Therapeutics LLC, No.IPR2015-00893, Paper 14 at 8 (PTAB Sept. 22, 2015).Furthermore, the Board has consistently held that under these circumstances,the question of whether an Examiner materially erred under Becton factor (e) cannotbe answered without evaluating whether the prior art challenge presented in thePetition demonstrates a likelihood of success on the merits. These cases find materialerror consistent with factor (e) when such a likelihood has been demonstrated. Seee.g, Skechers U.S.A., Inc. v. Nike, Inc., Paper 10 at 19-20 (PTAB May 19, 2021)(petitioner demonstrated material error by demonstrating a “reasonable likelihood ofprevailing” in its anticipation argument regarding a reference cited in an IDS but notsubstantively considered by the Examiner); HTC Corp. v. Motiva Patents, LLC,IPR2019-01666, Paper 9 at 10 (PTAB Apr. 3, 2020) (petitioner demonstrated amaterial error under the second part of the Advanced Bionics framework when tworeferences cited in an IDS but not substantively considered by the Examiner during10

prosecution disclosed all the limitations of the claims). The Board has alreadypreliminarily evaluated whether Dixon, Regeneron (8-May-2008), NCT-795, andNCT-377 teach the dosage regimen claimed in the ‘572 patent (as it’s the samedosage regimen claimed in the ‘338 patent), and found in the affirmative. SeeIPR2021-00881, Paper 21, Institution Decision at 28, 32 (November 10, 2021)(granting institution on claims covering the same dosage regimen based on groundsusing the same prior art).Accordingly, in view of the material error by the Examiner, the Board shouldnot exercise its discretion to deny institution.VI.THRESHOLD REQUIREMENT FOR INTER PARTES REVIEWThis Petition meets and exce

UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD APOTEX INC., Petitioner v. REGENERON PHARMACEUTICALS, INC., Patent Owner Inter Partes Review No.: IPR2022-01524 U.S. Patent No. 11,253,572 Filed: June 21, 2021 Issued: February 22, 2022 Inventor: George D. Yancopoulos . QUANTITATIVE BIOLOGY 411 (2005) ("Rudge .