Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 1 of 37 PageID #: 4874
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF WEST VIRGINIA
`CLARKSBURG DIVISION
`
`
`Plaintiff,
`
`
`v.
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`
`REGENERON PHARMACEUTICALS, INC.,
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`
`
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`MYLAN PHARMACEUTICALS INC.,
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`
`
`
`
`
`Case No. 1:22-cv-00061-TSK
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`JURY TRIAL DEMANDED
`
`
`
`
`
`
`
`Defendant.
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`
`
`
`
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`REGENERON’S OPENING CLAIM CONSTRUCTION BRIEF
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`

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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 2 of 37 PageID #: 4875
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`
`Table of Authorities ........................................................................................................................ ii
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`Table of Contents
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`I.
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`Legal Principles ......................................................................................................................1
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`II. The Formulation Patent...........................................................................................................4
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`A.
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`B.
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`“Organic Co-Solvent” ..............................................................................................5
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`“Present in Native Conformation . . . as Measured by Size Exclusion
`Chromatography” .....................................................................................................8
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`III. The Treatment Patents ..........................................................................................................12
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`A.
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`B.
`
`C.
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`“Best Corrected Visual Acuity” .............................................................................13
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`Patients Excluded from Treatment.........................................................................17
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`“Formulated as an Isotonic Solution” ....................................................................20
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`IV. The Manufacturing Patents ...................................................................................................22
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`A.
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`B.
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`C.
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`“Anti-oxidants” ......................................................................................................22
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`“Chemically Defined Medium (CDM)” ................................................................24
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`“Cell(s) Cultured in a Chemically Defined Medium (CDM)”...............................26
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`V. Conclusion ............................................................................................................................30
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`i
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 3 of 37 PageID #: 4876
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`
`Table of Authorities
`
`CASES
`
`Acumed LLC v. Stryker Corp.,
`483 F.3d 800 (Fed. Cir. 2007)....................................................................................................2
`
`Avid Tech., Inc. v. Harmonic, Inc.,
`812 F.3d 1040 (Fed. Cir. 2016)..................................................................................................8
`
`Cadence Pharmaceuticals Inc. v. Exela Pharmsci Inc.,
`780 F. 3d 1364 (Fed. Cir. 2015)...............................................................................................21
`
`Cias, Inc. v. Alliance Gaming Corp.,
`504 F.3d 1356 (Fed. Cir. 2007)................................................................................................28
`
`CR Bard Inc. v. AngioDynamics, Inc.,
`979 F.3d 1372 (Fed. Cir. 2020)................................................................................................19
`
`CUPP Comput. AS v. Trend Micro Inc.,
`-- F.4th --, 2022 WL 16954357 (Fed. Cir. Nov. 16, 2022) ........................................................7
`
`Curtiss-Wright Flow Control Corp. v. Velan, Inc.,
`438 F.3d 1374 (Fed. Cir. 2006)..................................................................................................5
`
`dunnhumby USA, LLC v. emnos USA Corp.,
`2015 WL 1542365 (N.D. Ill. Apr. 1, 2015) .............................................................................25
`
`Epistar Corp. v. ITC,
`566 F.3d 1321 (Fed. Cir. 2009)..................................................................................................2
`
`Game & Tech. Co., Ltd. v. Activision Blizzard Inc.,
`926 F. 3d 1370 (Fed. Cir. 2019)...............................................................................................28
`
`Gillette Co. v. Energizer Holdings, Inc.,
`405 F. 3d 1367 (Fed. Cir. 2005)...............................................................................................28
`
`Hill-Rom Servs., Inc. v. Stryker Corp.,
`755 F.3d 1367 (Fed. Cir. 2014)................................................................................................23
`
`In re Chatfield,
`545 F.2d 152 (CCPA 1976) .....................................................................................................18
`
`In re Distefano,
`808 F.3d 845 (Fed. Cir. 2015)..................................................................................................18
`
`Intamin Ltd. v. Magnetar Techs., Corp.,
`483 F.3d 1328 (Fed. Cir. 2007)................................................................................................23
`
`ii
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 4 of 37 PageID #: 4877
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`
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`
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`Intel Corp. v. Qualcomm Inc.,
`21 F.4th 801 (Fed. Cir. 2021) ..................................................................................................23
`
`Interactive Gift Exp., Inc. v. Compuserve, Inc.,
`256 F.3d 1323 (Fed. Cir. 2001)..................................................................................................9
`
`Invitrogen Corp v. Biocrest Mfg., LP,
`327 F.3d 1364 (Fed. Cir. 2003)..........................................................................................28, 29
`
`Laitram Corp. v. NEC Corp.,
`62 F.3d 1388 (Fed. Cir. 1995)....................................................................................................5
`
`Liebel-Flarsheim Co. v. Medrad, Inc.,
`358 F.3d 898 (Fed. Cir. 2004)....................................................................................................3
`
`Littelfuse, Inc. v. Mersen USA EP Corp.,
`29 F.4th 1376 (Fed. Cir. 2022) ................................................................................................23
`
`Markman v. Westview Instruments, Inc.,
`517 U.S. 370 (1996) ...................................................................................................................1
`
`Martek Biosciences Corp. v. Nutrinova, Inc.,
`579 F.3d 1363 (Fed. Cir. 2009)................................................................................................24
`
`Mformation Techs., Inc. v. Rsch. in Motion Ltd.,
`764 F.3d 1392 (Fed. Cir. 2014)............................................................................................2, 19
`
`MPHJ Tech. Investments, LLC v. Richo Ams. Corp.,
`847 F.3d 1363 (Fed. Cir. 2017)................................................................................................26
`
`Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co.,
`868 F.3d 1013 (Fed. Cir. 2017)..................................................................................................6
`
`O2 Micro Int’l Ltd. v. Beyond Innovation Tech. Co.,
`521 F. 3d 1351 (Fed. Cir. 2008).........................................................................................20, 23
`
`Ortho-McNeil Pharm., Inc. v. Mylan Lab’ys, Inc.,
`520 F.3d 1358 (Fed. Cir. 2008)................................................................................................14
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc)........................................................................ passim
`
`Praxair Distribution, Inc. v. Mallinckrodt Hosp. Prods. IP Ltd.,
`890 F.3d 1024 (Fed. Cir. 2018)....................................................................................18, 19, 20
`
`Rapoport v. Dement,
`254 F.3d 1053 (Fed. Cir. 2001)................................................................................................19
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`Teva Pharm. USA, Inc. v. Sandoz, Inc., 574 U.S. 318 (2015) .....................................................1, 4
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`iii
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 5 of 37 PageID #: 4878
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`
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`Thorner v. Sony Comput. Ent. Am. LLC,
`669 F.3d 1362 (Fed. Cir. 2012)............................................................................................3, 24
`
`Toshiba Corp. v. Imation Corp.,
`681 F.3d 1358 (Fed. Cir. 2012)............................................................................................3, 21
`
`Tr. of Columbia Univ. v. Symantec Corp.,
`811 F.3d 1359 (Fed. Cir. 2016)..................................................................................................7
`
`Trebro Mfg., Inc. v. FireFly Equip., LLC,
`748 F.3d 1159 (Fed. Cir. 2014)................................................................................................24
`
`U.S. Surgical Corp. v. Ethicon, Inc.,
`103 F.3d 1554 (Fed. Cir. 1997)........................................................................................1, 8, 12
`
`Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd.,
`887 F.3d 1117 (Fed. Cir. 2018)................................................................................................19
`
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996)..................................................................................................25
`
`Vivid Techs., Inc. v. Am. Sci. & Eng’g,
`200 F.3d 795 (Fed. Cir. 1999)................................................................................................1, 6
`
`STATUTES & REGULATIONS
`
`35 U.S.C. § 111 ..............................................................................................................................26
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`35 U.S.C. § 112, ¶ 4 ........................................................................................................................5
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`35 U.S.C. § 112(d) ...........................................................................................................................5
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`35 U.S.C. § 271(e)(1) .....................................................................................................................14
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`37 C.F.R. § 1.75 ...............................................................................................................................2
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`OTHER AUTHORITIES
`
`Manual for Patent Examining and Procedure ................................................................................28
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`
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`iv
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 6 of 37 PageID #: 4879
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`These proceedings concern aflibercept, the active ingredient in Regeneron’s flagship
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`product EYLEA®. Aflibercept works by binding to a protein called “VEGF.” VEGF’s normal
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`role in the body is to trigger the growth of blood vessels, also known as “angiogenesis.” But too
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`much VEGF, and too much resulting blood vessel growth in the eye, can cause vision loss and
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`even blindness. Millions of patients, most of them elderly, suffer from VEGF-related eye
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`diseases, including wet age-related macular degeneration (“AMD”) and diabetic macular edema.
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`By binding to VEGF in the eye, aflibercept can treat those and other diseases.
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`The initial proceedings in this case are focused on three sets of inventions. One patent
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`concerns the “drug product,” the actual solution in a vial that maintains the drug’s stability for
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`months. Two patents concern aflibercept’s use, and specifically, how much and how often the
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`drug should be administered to permit more time between doses than patients enjoyed with
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`previous treatments while achieving therapeutic gains. The final three patents concern methods
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`for making aflibercept arising from Regeneron’s efforts to improve how to make the drug.
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`The parties have identified various claim construction issues, narrowed their disputes
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`through conferral, and memorialized their stipulations and disagreements about the scope of
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`Regeneron’s patent rights in the Joint Claim Construction Chart, ECF No. 102. These legal
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`disputes are for the Court to resolve, Markman v. Westview Instruments, Inc., 517 U.S. 370, 388-
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`89 (1996), but only “to the extent necessary to resolve the [parties’] controversy” about claim
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`scope, Vivid Techs., Inc. v. Am. Sci. & Eng’g, 200 F.3d 795, 803 (Fed. Cir. 1999). The Court
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`should adopt Regeneron’s proposed constructions for the reasons set forth below.
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`I.
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`Legal Principles
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`Claim construction is the process by which the Court gives legal effect to the meaning of
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`the claims. See Teva Pharm. USA, Inc. v. Sandoz, Inc., 574 U.S. 318, 321-22 (2015). “It is not
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`1
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 7 of 37 PageID #: 4880
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`an obligatory exercise in redundancy” and is not required where a term’s meaning is apparent
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`from the claim language itself or its scope is not disputed. U.S. Surgical Corp. v. Ethicon, Inc.,
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`103 F.3d 1554, 1568 (Fed. Cir. 1997). “Some line-drawing problems . . . [are] properly left to
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`the trier of fact.” Acumed LLC v. Stryker Corp., 483 F.3d 800, 806 (Fed. Cir. 2007).
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`The Federal Circuit’s leading authority on how to construe claims, Phillips v. AWH
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`Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc), instructs district courts to proceed through a
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`canonical hierarchy of evidence: first the claims, then the patent’s specification, then its
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`prosecution history, and finally any “extrinsic” evidence. To begin, “[i]t is a ‘bedrock principle’
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`of patent law that ‘the claims of a patent define the invention.’” Id. at 1312. “[T]he claims
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`themselves provide substantial guidance as to the meaning of particular claim terms” and “the
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`context in which a term is used in the asserted claim can be highly instructive.” Id. at 1314.
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`This is true for both the claim containing the disputed term itself, as well as all other claims in
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`the patent—whether asserted or unasserted. Id. “For example, the presence of a dependent
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`claim that adds a particular limitation gives rise to a presumption that the limitation in question is
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`not present in the independent claim.”1 Id. at 1314-15. By the same token, courts should avoid
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`constructions that render a limitation in any claim “redundant,” id. at 1324-25, or “superfluous,”
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`Mformation Techs., Inc. v. Rsch. in Motion Ltd., 764 F.3d 1392, 1399 (Fed. Cir. 2014).
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`“[T]he words of a claim ‘are generally given their ordinary and customary meaning,’”
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`which is “the meaning that the term would have to a person of ordinary skill in the art
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`[(“POSA”)] in question at the time of the invention, i.e., as of the effective filing date of the
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`patent application.” Phillips, 415 F.3d at 1312-13. There is a “heavy presumption” that “claim
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`1 An “independent” claim is a standalone claim that contains all the limitations that define an invention,
`whereas a “dependent” claim refers back to, and incorporates by dependency, a previous independent
`claim and further limits the claim. See generally 37 C.F.R. § 1.75.
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`2
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`

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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 8 of 37 PageID #: 4881
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`terms carry their full ordinary and customary meaning.” Epistar Corp. v. ITC, 566 F.3d 1321,
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`1334 (Fed. Cir. 2009). Thus, a patentee is “free to choose a broad term and expect to obtain the
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`full scope of its plain and ordinary meaning.” Thorner v. Sony Comput. Ent. Am. LLC, 669 F.3d
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`1362, 1367 (Fed. Cir. 2012). A court may depart from that meaning in only two instances:
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`“lexicography” or “disavowal.” Id. at 1365-66; Toshiba Corp. v. Imation Corp., 681 F.3d 1358,
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`1369 (Fed. Cir. 2012). The lexicography exception applies when a patentee “‘clearly set[s] forth
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`a definition of the disputed claim term’ other than its plain and ordinary meaning,” in the
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`specification or prosecution history, and “‘clearly express[es] an intent’ to redefine the term.”
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`Thorner, 669 F.3d at 1365. Disavowal requires the specification or prosecution history
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`unambiguously to make “clear that the invention does not include a particular feature.” Id.
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`Beyond the claims themselves, “the specification ‘is always highly relevant to the claim
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`construction analysis. Usually, it is dispositive; it is the single best guide to the meaning of a
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`disputed term.’” Phillips, 415 F.3d at 1315. But while the specification serves as a resource to
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`understand the words used in the claims, courts must avoid the “cardinal sin” of importing
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`language from the specification into the claims. Id. at 1320. Indeed, even if every example
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`described in the specification contains a particular element, such uniformity is not enough to
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`justify importing that element into claims whose plain language does not expressly require it.
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`See id. at 1323; Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898, 906-07 (Fed. Cir. 2004).
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`“[A] court ‘should also consider the patent’s prosecution history.’” Phillips, 415 F.3d at
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`1317. “Yet because the prosecution history represents an ongoing negotiation between the PTO
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`and the applicant, rather than the final product of that negotiation, it often lacks the clarity of the
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`specification and thus is less useful for claim construction purposes.” Id.
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`Sometimes, a “court will need to look beyond the patent’s intrinsic evidence and to
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`3
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 9 of 37 PageID #: 4882
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`consult extrinsic evidence in order to understand, for example, the background science or the
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`meaning of a term in the relevant art during the relevant time period.” Teva Pharm., 574 U.S. at
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`331. When claim construction “involves little more than the application of the widely accepted
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`meaning of commonly understood words[,] . . . general purpose dictionaries may be helpful.”
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`Phillips, 415 F.3d at 1314. But extrinsic evidence cannot be used to “contradict claim meaning
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`that is unambiguous in light of the intrinsic evidence.” Id. at 1318-19, 1324.
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`II.
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`The Formulation Patent
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`U.S. Patent No. 11,084,865 (Ex. 1) claims an EYLEA drug product, i.e., a “vial”
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`containing an “ophthalmic formulation” that is “suitable for intravitreal administration.” ’865
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`patent, claim 1. “[I]ntravitreal administration” refers to how the formulation is injected into the
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`eye. As relevant here, EYLEA is injected into the vitreous and diffuses into the back of the
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`eye—where the retina is located and where aflibercept is therapeutically active. The claimed
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`ophthalmic formulation comprises several components: a VEGF antagonist2 with a specific
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`sequence,3 “an organic co-solvent,” a buffer, and a stabilizing agent. The claim further requires
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`that the formulation possess a particular type of stability measured in a specific way: at least 98%
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`of the VEGF antagonist must be “present in native conformation following storage at 5° C. for
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`two months as measured by size exclusion chromatography.”
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`The parties have two disputes with respect to the ’865 patent: what constitutes an
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`“organic co-solvent” and what it means for the aflibercept to be “present in native
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`conformation . . . as measured by size exclusion chromatography.”
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`2 Compounds that bind to and counteract VEGF are known as “VEGF antagonists.”
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`3 The limitation “amino acids 27-457 of SEQ ID NO:4” describes the “amino acid sequence” of the
`VEGF antagonist and corresponds to the sequence of the aflibercept protein.
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`4
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 10 of 37 PageID #: 4883
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`A.
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`“Organic Co-Solvent”
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`Regeneron’s Proposed Construction
`Plain and ordinary meaning in view of the
`claims and specification; to the extent there is
`a dispute as to claim scope, “organic co-
`solvent” includes polysorbate 20, polysorbate
`80, polyethylene glycol, or propylene glycol,
`or a combination thereof
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`
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`Mylan’s Proposed Construction
`an organic substance added to a primary
`solvent to increase the solubility of said
`VEGF antagonist
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`The parties dispute whether the substances specifically listed in the patent as “organic co-
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`solvents” are in fact “organic co-solvents.” Under Mylan’s proposal, despite being specifically
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`listed as “organic co-solvents” in the claims and specification, these substances somehow could
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`be excluded from the scope of that term. But the claims and specification leave no doubt that the
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`listed substances like polysorbate are “organic co-solvents.”
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`The dependent claims resolve this dispute, expressly claiming that the “organic co-
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`solvent” is “polysorbate.” “[D]ependent claims can aid in interpreting the scope of claims from
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`which they depend,” Laitram Corp. v. NEC Corp., 62 F.3d 1388, 1392 (Fed. Cir. 1995), because
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`independent claims necessarily must cover the entirety of the subject matter of claims that
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`depend from them. See Curtiss-Wright Flow Control Corp. v. Velan, Inc., 438 F.3d 1374, 1380
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`(Fed. Cir. 2006) (“[T]he statute stresses that a dependent claim must add a limitation to those
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`recited in the independent claim.” (emphasis added) (citing 35 U.S.C. § 112, ¶ 4 (now
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`§ 112(d)))). In Laitram, for example, the Federal Circuit reasoned that because a dependent
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`claim recited a particular embodiment (a printer that “strobes”), that embodiment must also be
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`covered by the broader independent claim. Id. at 1392-93. The same result obtains here: claim 2
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`depends from claim 1 and recites specifically that “said organic co-solvent comprises
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`polysorbate”; claims 4-5 depend from claim 2 and more specifically recite that “said organic co-
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`solvent” comprises an amount of “polysorbate 20.” It thus follows as a matter of law that the
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`5
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 11 of 37 PageID #: 4884
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`“organic co-solvent” in claim 1 must include polysorbate (and more).
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`The specification reinforces this point. As “the single best guide to the meaning of a
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`disputed term,” Phillips, 415 F.3d at 1315, its guidance here is unequivocal: “the organic co-
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`solvent may be polysorbate, for example, polysorbate 20 or polysorbate 80, polyethylene glycol
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`(PEG), for example, PEG 3350, or propylene glycol, or a combination thereof.” ’865 patent,
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`2:39-42. Though once would be enough, the specification repeatedly confirms that substances
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`like polysorbate are organic co-solvents. ’865 patent, 2:39-40, 2:49-50, 3:28-30, 4:16-17, 7:5.
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`Resolving the parties’ claim construction dispute concerning “organic co-solvent” thus
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`requires no more than acknowledging what the claims and specification state clearly: polysorbate
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`is an organic co-solvent. Courts construe claims “only to the extent necessary to resolve the
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`[parties’] controversy,” which is whether “organic co-solvent” includes or excludes polysorbate,
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`and there is no need for the Court to consider what additional substances this claim term
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`encompasses
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`. Nidec Motor Corp. v.
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`Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017). While the Court
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`must construe the claims “objectively” in view of the intrinsic record “and without reference to
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`the accused device,” the parties have a simple dispute as to claim scope—whether polysorbate,
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`one of the specification’s listed organic co-solvents, is within the meaning of “organic co-
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`solvent.” Vivid Techs., Inc., 200 F.3d at 803. Mylan’s
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` explains why the
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`parties contest the meaning of “organic co-solvent” and essentially frames the dispute requiring
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`the Court’s resolution.
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`Mylan contends that whether polysorbate is an organic co-solvent depends on why and
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`how it was added to the formulation. This construction defies the patent’s repeated and
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`unequivocal guidance—the words of Mylan’s construction are found nowhere in the
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`6
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 12 of 37 PageID #: 4885
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`specification. “The only meaning that matters in claim construction is the meaning in the context
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`of the patent,” and the patent could not be clearer that polysorbate is an organic co-solvent. Tr.
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`of Columbia Univ. v. Symantec Corp., 811 F.3d 1359, 1363 (Fed. Cir. 2016) (emphasis added).
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`To the extent Mylan seeks to rely on extrinsic evidence to the contrary, such evidence cannot
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`trump the claims’ and specification’s clear guidance. Phillips, 415 F.3d at 1318.
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`Further, while the claim language and specification suffice to end the inquiry, Mylan’s
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`proposed construction suffers additional defects. Under Mylan’s proposed construction, a
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`substance would only count as an “organic co-solvent” if it satisfies two functional requirements:
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`that the organic co-solvent (1) is “added to a primary solvent,” (2) “to increase the solubility of
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`said VEGF antagonist.” Neither requirement finds any support in either the plain language of the
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`claims or the specification, and both are contrary to Federal Circuit precedent.
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`First, the specification nowhere teaches that an organic co-solvent must be “added to a
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`primary solvent”—indeed, the patent never uses the phrase “primary solvent” at all. And in most
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`of the examples (1, 3-8), polysorbate is the only organic co-solvent. ’865 patent, 8:33-12:13. If,
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`as Mylan contends, polysorbate is not an organic co-solvent, then each of these embodiments is
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`not covered by the patent. But “a claim interpretation that excludes a preferred embodiment
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`from the scope of the claim is rarely, if ever, correct.” CUPP Comput. AS v. Trend Micro Inc., --
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`F.4th --, 2022 WL 16954357, at *3 (Fed. Cir. Nov. 16, 2022). It is surely incorrect here.
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`Second, the specification nowhere suggests that an “organic co-solvent” must “increase
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`the solubility of said VEGF antagonist.” Under Mylan’s construction, a substance would be an
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`“organic co-solvent” in some circumstances but not in others. That is contrary to the term’s
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`usage in the specification, which simply lists examples of substances that are organic co-solvents
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`generally, without evaluating whether those substances increase the solubility of a VEGF
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`7
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`Case 1:22-cv-00061-TSK Document 124 Filed 11/29/22 Page 13 of 37 PageID #: 4886
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`antagonist in a particular formulation. ’865 patent, 2:39-42, 3:28-31, 4:15-17, 7:5-7. In this
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`respect, Mylan’s proposed construction violates (another) principle of claim construction by
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`introducing confusion and uncertainty into the meaning of a claim term where it otherwise would
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`not exist. As the Federal Circuit has explained, the core purpose of claim construction is “to
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`clarify” claim scope, U.S. Surgical, 103 F.3d at 1568, so that “the finder of fact [has] an
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`understandable interpretation of claim scope to apply to the accused [product],” Avid Tech., Inc.
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`v. Harmonic, Inc., 812 F.3d 1040, 1050 (Fed. Cir. 2016). By inventing a functional test nowhere
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`disclosed in the specification that would make a substance an “organic co-solvent” for some
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`formulations but not for others, Mylan’s proposed construction confounds rather than clarifies.
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`B.
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`“Present in Native Conformation . . . as Measured by Size Exclusion
`Chromatography”
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`Mylan’s Proposed Construction
`Plain and ordinary meaning:
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`[present in] a form that does not exhibit
`chemical or physical instability
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`Regeneron’s Proposed Construction
`This term does not need to be construed
`outside of the context of the limitations in
`which it appears (e.g., “wherein at least 98%
`of the VEGF antagonist is present in native
`conformation following storage at 5° C. for
`two months as measured by size exclusion
`chromatography.”). Within that context, it
`should be given its plain and ordinary
`meaning in view of the claims and the
`specification
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`The Court should construe the phrase “present in native conformation” in the context of
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`the limitation in which it appears, which recites specifically that the VEGF antagonist is “present
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`in native conformation following storage at 5° C. for two months as measured by size exclusion
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`chromatography.” ’865 patent, claim 1 (emphasis added). The complete claim language
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`instructs the reader how to determine whether the VEGF antagonist is “present in native
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`conformation,” and no further construction is necessary. Mylan’s proposed construction is
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`wrong for two reasons: (1) it obscures the specific way in which “native conformation” is
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`measured in the ’865 patent, and (2) it introduces a vague functional limitation encompassing
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`unspecified types of “chemical or physical []stability” that are not recited in the claims and
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`would not be measured by size exclusion chromatography.
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`The claim construction inquiry “must begin and remain centered on the language of the
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`claims themselves.” Interactive Gift Exp., Inc. v. Compuserve, Inc., 256 F.3d 1323, 1331 (Fed.
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`Cir. 2001); Phillips, 415 F.3d at 1314. And in interpreting the claim language, “the context of
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`the surrounding words of the claim . . . must be considered in determining the ordinary and
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`customary meaning of those terms.” Phillips, 415 F.3d at 1314 (quoting ACTV, Inc. v. Walt
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`Disney Co., 346 F.3d 1082, 1088 (Fed. Cir. 2003)). That context here is essential, because it
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`specifies precisely how “native conformation” is “measured”: by “size exclusion
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`chromatography.” ’865 patent, claim 1. In view of this context, “present in native
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`conformation” does not require further construction. Mylan, in contrast, seeks to construe
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`“native conformation” in isolation from the surrounding claim language and as requiring various
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`types of stability untethered to the particular assay recited in the claims. That would be error.
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`Contrary to Mylan’s proposed construction, the claims do not recite that “native
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`conformation” is a catch-all phrase relating to all forms of “chemical and physical instability.”
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`Nor does the specification. Although the ’865 patent provides a “general description” explaining
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`that proteins may exhibit both “[c]hemical instability” and “[p]hysical instability,” the
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`specification does not equate these general concepts to the claimed “native conformation”
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`measured by size exclusion chromatography. ’865 patent, 5:51-60. The specification does not
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`even mention “native conformation” in this passage. Id. Rather, it explains that there are
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`multiple attributes of protein stability, ’865 patent, 5:51-60, and various methods for evaluating
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`different aspects of protein stability, id. at 7:8-19 (listing, among others, “UV spectroscopy,”
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`“SDS -PAGE,” and “isoaspartate quantification”). But these various stability attributes and
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`means for assessing them are absent from the claims, which recite neither “chemical” nor
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`“physical” stability. Claim 1 recites just one attribute and one measurement technique: that the
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`VEGF antagonist is “present in native conformation . . . as measured by size exclusion
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`chromatography.” “[S]ize exclusion chromatography” does not measure all types of stability—
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`rather, it is a technique used specifically to separate molecules of different size.4 Size exclusion
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`chromatography is used to separate “native proteins” from “aggregated proteins,” i.e.,
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`significantly larger clumps formed by several proteins sticking together. Roufik at 235. That is
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`how size exclusion chromatography is used in the ’865 patent—to detect the amount of protein
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`in “native” conformation. But the technique has limitations: “A 50–100% difference in
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`molecular weight is typically required” for separation by size exclusion chromatography. Goetz
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`at 287. The types of instability that Mylan’s construction attempts to smuggle into the claims,
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`such as “deamination” and “oxidation of methionine residues,” ’865 patent, 5:57-58, refer to
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`minute changes in the structure of the protein that are not detectable by size exclusion
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`chromatography. Mylan’s construction thus makes no sense, as it encompasses changes to the
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`VEGF protein that are not detected by the analytical technique expressly referenced in the claim.
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`The specification’s disclosure relevant to “native conformation” does not refer to
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`“physical” or “chemical” instability generally. Rather, the patent explains that size exclusion
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`chromatography (specifically, “size exclusion HPLC”) was used to evaluate the VEGF
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`antagonist’s “purity,” which the patent refers to in da