Case: 19-2418 Document: 67 Page: 1 Filed: 03/01/2021
`
`
`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`BAYER HEALTHCARE LLC,
`Plaintiff-Cross-Appellant
`
`v.
`
`BAXALTA INC., BAXALTA US INC.,
`Defendants-Appellants
`
`NEKTAR THERAPEUTICS,
`Defendant-Appellee
`______________________
`
`2019-2418, 2020-1017
`______________________
`
`Appeals from the United States District Court for the
`District of Delaware in No. 1:16-cv-01122-RGA, Judge
`Richard G. Andrews.
`______________________
`
`Decided: March 1, 2021
`______________________
`
`BRADFORD J. BADKE, Sidley Austin LLP, New York,
`NY, argued for plaintiff-cross-appellant. Also represented
`by SONA DE, CHING-LEE FUKUDA; JOSHUA JOHN FOUGERE,
`RYAN C. MORRIS, PAUL ZEGGER, Washington, DC.
`
` EDGAR HAUG, Haug Partners LLP, New York, NY, ar-
`gued for defendants-appellants and defendant-appellee.
`Also represented by KAITLIN ABRAMS, NICHOLAS F. GIOVE,
`JONATHAN HERSTOFF, ERIKA SELLI.
`
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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` ______________________
`
`Before NEWMAN, LINN, and STOLL, Circuit Judges.
`STOLL, Circuit Judge.
`This patent infringement case presents various issues
`of claim scope, infringement, validity, and damages. Bayer
`HealthCare LLC sued Baxalta Inc. and Baxalta US Inc.
`(collectively, “Baxalta”) and Nektar Therapeutics, alleging
`that Baxalta’s biologic product Adynovate® infringes cer-
`tain claims of Bayer’s U.S. Patent No. 9,364,520. The jury
`found that the asserted claims were enabled and infringed,
`and that Bayer was entitled to reasonable-royalty dam-
`ages. The district court did not, however, send the question
`of willful infringement to the jury, instead holding as a
`matter of law that Baxalta’s conduct did not meet the re-
`quirements for willfulness. Baxalta now appeals the dis-
`trict court’s denial of its motions for judgment as a matter
`of law or a new trial on the issues of infringement, enable-
`ment, and damages, along with the court’s award of pre-
`verdict supplemental damages. Bayer cross-appeals, chal-
`lenging the district court’s denial of its motion for a new
`trial on willfulness. We affirm.
`BACKGROUND
`I
`The ’520 patent is directed to recombinant forms of hu-
`man factor VIII (or FVIII). FVIII is a protein that is pro-
`duced, and released into the bloodstream, by the liver.
`FVIII comprises 2,332 amino acids and has six different
`structural domains: A1-A2-B-A3-C1-C2. Most relevant to
`this case is the domain of FVIII known as the “B-domain.”
`As “a critical component of the intrinsic pathway of
`blood coagulation,” FVIII is useful in the treatment of he-
`mophilia A. ’520 patent col. 1 ll. 29–30. Hemophilia A is
`the “most common hereditary coagulation disorder” and is
`“caused by deficiency or structural defects in” naturally
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`occurring FVIII. Id. at col. 1 ll. 27–29. Because FVIII has
`a “short half-life” of “only about 11 hours,” as a therapeutic
`it “must be administered frequently.” Id. at col. 1 ll. 52–55.
`The ’520 patent recognizes that “[t]he need for frequent in-
`travenous injection creates tremendous barriers to patient
`compliance” and, thus, “[i]t would be more convenient for
`the patients if a FVIII product could be developed that had
`a longer half-life and therefore required less frequent ad-
`ministration.” Id. at col. 1 ll. 56–60; see id. at col. 2
`ll. 47– 49. Moreover, “the cost of treatment could be re-
`duced if the half-life were increased because fewer dosages
`may then be required.” Id. at col. 1 ll. 60–62.
`The patent explains that a process called “PEGylation”
`has “been demonstrated to increase the in vivo half-life of
`a protein.” Id. at col. 3 ll. 34–35. PEGylation is the conju-
`gation (or attachment) of a polymer called polyethylene gly-
`col (PEG) to a protein such as FVIII. See id. at col. 3
`ll. 35– 37; see also id. at col. 9 ll. 12–14. PEG is a type of
`polyalkylene oxide. See id. at col. 8 ll. 41–43.
`The patent further teaches that “random” modification
`of FVIII by PEGylation was known and that certain ran-
`domly PEGylated proteins had been approved as therapeu-
`tics. The inventors sought, however, “a more specific
`method for PEGylating FVIII” because the prior-art “ran-
`dom” approach had several drawbacks:
`Random modification of FVIII by targeting pri-
`mary amines (N-terminus and lysines) with large
`polymers such as PEG and dextran has been at-
`tempted with varying degree[s] of success . . . .
`This random approach . . . is much more problem-
`atic for the heterodimeric FVIII. FVIII has hun-
`dreds of potential PEGylation sites, including the
`158 lysines, the two N-termini, and multiple histi-
`dines, serines, threonines, and tyrosines, all of
`which could potentially be PEGylated with rea-
`gents primarily targeting primary amines.
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`Id. at col. 3 l. 50–col. 4 l. 1, col. 4 ll. 19–20.
`The patent identifies as an “additional drawback to not
`controlling the site of PEGylation on FVIII” the “potential
`activity reduction if the PEG were to be attached at or near
`critical active sites, especially if more than one PEG or a
`single large PEG is conjugated to FVIII.” Id. at col. 4
`ll. 7– 11. Furthermore, “[b]ecause random PEGylation will
`invariably produce large amounts of multiply PEGylated
`products, purification to obtain only mono-PEGylated
`products will drastically lower overall yield.” Id. at col. 4
`ll. 11–14. Finally, the patent explains that “the enormous
`heterogeneity in product profile will make consistent syn-
`thesis and characterization of each lot nearly impossible”
`and constitutes “a barrier to commercialization,” since
`“good manufacturing requires a consistent, well-character-
`ized product.” Id. at col. 4 ll. 14–19; see id. at col. 4 ll. 4–7
`(“[H]eterogeneous processing of full length FVIII can lead
`to a mixture of starting material that leads to further com-
`plexity in the PEGylated products.”).
`Thus, the inventors recognized “a need for an improved
`FVIII variant that possesses greater duration of action in
`vivo . . . while retaining functional activity,” and that is de-
`sirably “produced as a homogeneous product in a consistent
`manner.” Id. at col. 4 l. 65–col. 5 l. 3. The patent purports
`to overcome the drawbacks of “random” PEGylation by us-
`ing “site-directed” PEGylation at the B- domain of FVIII:
`The present invention is based on the discovery
`that polypeptides having FVIII activity can be co-
`valently attached at a predefined site to a biocom-
`patible polymer that is not at an N-terminal amine,
`and that such polypeptides substantially retain
`their coagulant activity. Furthermore, these poly-
`peptide conjugates have improved circulation time
`and reduced antigenicity. The conjugates of the in-
`vention are advantageous over the prior art conju-
`gates that had random polymer attachments to
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`FVIII or attachments at an N-terminal. Site-di-
`rected attachment allows one to design modifica-
`tions that avoid the regions required for biological
`activity and thereby to maintain substantial FVIII
`activity. . . . Site-directed attachment also allows
`for a uniform product rather than the heterogene-
`ous conjugates produced in the art by random pol-
`ymer coupling.
`Id. at col. 8 ll. 15–30; see id. at col. 15 ll. 9– 13 (explaining
`that the “retained activity” of the claimed conjugates was
`“surprising” given “the problems with past polymeric con-
`jugates causing nonspecific addition and reduced activity”).
`Claim 1 is the only asserted independent claim and re-
`cites:
`1. An isolated polypeptide conjugate comprising a
`functional factor VIII polypeptide and one or more
`biocompatible polymers, wherein the functional
`factor VIII polypeptide comprises the amino acid
`sequence of SEQ ID NO: 4 or an allelic variant
`thereof and has a B-domain, and further wherein
`the biocompatible polymer comprises polyalkylene
`oxide and is covalently attached to the functional
`factor VIII polypeptide at the B-domain.
`Id. at col. 61 ll. 9–16 (emphases added to the disputed claim
`terms).
`
`II
`Bayer sued Baxalta and Nektar, Baxalta’s collaborator
`on its Adynovate® product, for patent infringement. Ady-
`novate® is a recombinant PEGylated FVIII product used to
`treat hemophilia A. Adynovate® is made by PEGylating to
`amino acids in FVIII that have amine groups, including the
`amino acid lysine. We hereafter refer to this process as
`“amine/lysine” PEGylation.
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`The district court construed the claim term “an isolated
`polypeptide conjugate” in claim 1 to mean “a polypeptide
`conjugate where conjugation was not random.” Bayer
`Healthcare LLC v. Baxalta Inc., No. 16-cv-1122, 2018 WL
`3212425, at *2 (D. Del. June 29, 2018) (Claim Construction
`Op.). The district court determined that, during prosecu-
`tion of the ’520 patent, Bayer had “clearly and unmistaka-
`bly disclaimed any
`‘polypeptide
`conjugate where
`conjugation was random.’” Id. at *4.
`In addition, the district court construed the claim term
`“at the B-domain” in claim 1 to mean “attachment at the
`B- domain such that the resulting conjugate retains func-
`tional factor VIII activity.” Id. at *8. The district court re-
`jected Baxalta’s proposed construction of the term to mean
`“at a site that is not any amine or carboxy site in factor VIII
`and is in the B-domain,” finding that Bayer did not dis-
`claim PEGylation at amine or carboxy sites. Id. at *8–9.
`Baxalta moved for summary judgment of noninfringe-
`ment and invalidity for lack of enablement. The district
`court denied Baxalta’s motions due to genuine factual dis-
`putes. See Bayer HealthCare LLC v. Baxalta Inc.,
`No. 16- cv-1122, 2018 WL 6727054, at *3–7 (D. Del. Dec. 21,
`2018) (Summ. J. Op.). Baxalta also moved in limine re-
`questing that the district court clarify the meaning of “ran-
`dom” in its construction of “an isolated polypeptide
`conjugate.” The district court denied Baxalta’s motion,
`“again reject[ing] [Baxalta’s] argument that [Bayer] de-
`fined ‘random’ conjugation as ‘any conjugation at amines or
`carboxy sites.’” Bayer HealthCare LLC v. Baxalta Inc.,
`No. 16-cv-1122, 2019 WL 10890386, at *1 (D. Del. Jan. 3,
`2019) (Mot. in Lim. Order).
`Prior to trial, Baxalta moved to exclude the testimony
`of Bayer’s damages expert, Dr. Addanki, regarding his pro-
`posed reasonable-royalty rate. In his expert report, Dr. Ad-
`danki opined that Bayer was entitled to a royalty rate of
`23.75%—the midpoint of the bargaining range of 5.1% to
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`42.4%—based on the Nash Bargaining Solution. The dis-
`trict court concluded that the expert failed to tie his 50/50
`split to the facts of the case, and thus excluded his “opinion
`that a reasonable royalty rate is ‘the mid-point of the bar-
`gaining range’ . . . , including any subsequent opinions that
`rely on that mid-point rate.” Bayer HealthCare LLC v. Bax-
`alta Inc., No. 16-cv-1122, 2019 WL 330149, at *8 (D. Del.
`Jan. 25, 2019) (Daubert Order). The district court denied,
`however, Baxalta’s request to prohibit Dr. Addanki from
`testifying as to his proposed bargaining range of 5.1% to
`42.4%.
`The case then proceeded to a jury trial. The district
`court granted Baxalta’s pre-verdict motion for JMOL of no
`willful infringement. Thereafter, the jury found that Bax-
`alta infringed asserted claims 1–3 and 8 of the ’520 patent,
`and that none of those claims were invalid for lack of ena-
`blement. J.A. 1889–90, 1892. The jury also found that
`Bayer was entitled to $155,190,264 in reasonable-royalty
`damages for the time period from June 14, 2016 through
`November 30, 2018 based on a 17.78% royalty rate applied
`to a $872,836,128 royalty base. J.A. 1893.
`Following the verdict, Baxalta moved for JMOL or a
`new trial on the issues of infringement, enablement, and
`damages. The district court denied Baxalta’s motions. See
`generally Bayer Healthcare LLC v. Baxalta Inc.,
`407 F. Supp. 3d 462 (D. Del. 2019) (JMOL Op.). For its
`part, Bayer moved under Rule 59 of the Federal Rules of
`Civil Procedure for an award of pre-verdict supplemental
`damages for the time period from December 1, 2018
`through February 8, 2019, the date of the district court’s
`judgment. The district court granted Bayer’s motion and
`awarded Bayer supplemental damages in the amount of
`$18,324,562 based on the actual sales data for that period
`and the jury’s 17.78% royalty rate. Bayer Healthcare LLC
`v. Baxalta Inc., No. 16-cv-1122, 2019 WL 4016235, at *6
`(D. Del. Aug. 26, 2019) (Rule 59 Op.); Final Judgment at 2,
`Bayer Healthcare LLC v. Baxalta Inc., No. 16-cv-1122
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`(D. Del. Sept. 10, 2019), ECF No. 507. Bayer also moved
`for a new trial under Rule 59(a) on the issue of willfulness,
`but the district court denied its motion. Rule 59 Op.,
`2019 WL 4016235, at *8–9.
`Bayer and Baxalta appeal. We have jurisdiction pur-
`suant to 28 U.S.C. § 1295(a)(1).
`DISCUSSION
`This case presents various issues on appeal and cross-
`appeal. We start by addressing Baxalta’s challenges to the
`district court’s construction of the claim term “at the B-do-
`main” and its interpretation of the word “random” in its
`construction of the claim term “an isolated polypeptide con-
`jugate.” We then turn to Baxalta’s challenges to the dis-
`trict court’s judgments of infringement and enablement,
`along with the court’s awards of damages and pre-verdict
`supplemental damages. Finally, we address Bayer’s chal-
`lenge to the district court’s judgment of no willful infringe-
`ment.
`
`I
`We first address Baxalta’s challenge to the district
`court’s construction of the disputed term “at the B-domain”
`in claim 1. Baxalta contends that the district court erred
`in failing to construe the term to exclude amine/lysine con-
`jugation. Neither the parties nor the district court consid-
`ered extrinsic evidence in construing this claim term.
`“Claim construction based on the intrinsic evidence is a
`question of law that this court reviews de novo.” Hologic,
`Inc. v. Minerva Surgical, Inc., 957 F.3d 1256, 1269
`(Fed. Cir. 2020) (citing Trs. of Columbia Univ. v. Symantec
`Corp., 811 F.3d 1359, 1362 (Fed. Cir. 2016)). “The con-
`struction of claim terms based on the claim language, the
`specification, and the prosecution history are legal deter-
`minations.” Id. (quoting Trs. of Columbia Univ., 811 F.3d
`at 1362). Based on our review of the claim language, spec-
`ification, and prosecution history, we conclude that the
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`district court did not err in construing the disputed claim
`term.
`
`A
`The plain claim language recites “[a]n isolated polypep-
`tide conjugate” in which PEG “is covalently attached to the
`functional factor VIII polypeptide at the B-domain.” The
`plain language of claim 1 does not require PEGylation at
`any particular amino acid sites in the B-domain, let alone
`exclude from its scope any specific amino acids as attach-
`ment sites in the B-domain. Rather, claim 1 more broadly
`requires PEGylation at the B-domain as a region.
`B
`Statements in the specification support this view of the
`claims and indicate that site-directed PEGylation target-
`ing the B-domain, rather than particular amino acid sites
`within it, achieved the desired benefit of retaining coagu-
`lation activity. See, e.g., ’520 patent col. 4 ll. 7–9 (“An ad-
`ditional drawback to not controlling the site of PEGylation
`on FVIII is a potential activity reduction if the PEG were
`to be attached at or near critical active sites . . . .”); id.
`at col. 8 ll. 23–26 (“Site-directed attachment allows one to
`design modifications that avoid the regions required for bi-
`ological activity and thereby to maintain substantial FVIII
`activity.”). We acknowledge that the specification discloses
`embodiments of site-directed PEGylation at cysteine amino
`acids within the B- domain. See, e.g., id. at col. 5 ll. 46–57,
`col. 20 l. 56–col. 21 l. 5. But the specification does not state
`that this is the only embodiment or otherwise indicate that
`the invention is limited to site-directed PEGylation at cys-
`teine amino acids within the B-domain and, as noted above,
`the claim language is not so limited.
`On appeal, Baxalta contends that the specification dis-
`parages amine/lysine conjugation. In particular, it points
`to the “Background of the Invention,” which discloses that
`“[r]andom modification of FVIII by targeting primary
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`amines (N-terminus and lysines) with large polymers such
`as PEG” has “been attempted with varying degrees of suc-
`cess,” and that “[t]his random approach, however, is much
`more problematic” because FVIII has “hundreds of poten-
`tial PEGylation sites.” Appellants’ Br. 24 (quoting ’520 pa-
`tent col. 3 l. 50–col. 4 l. 1). To support its disparagement
`argument, Baxalta cites Indivior Inc. v. Dr. Reddy’s Labor-
`atories, S.A., 930 F.3d 1325 (Fed. Cir. 2019), and SciMed
`Life Systems, Inc. v. Advanced Cardiovascular Systems,
`Inc., 242 F.3d 1337 (Fed. Cir. 2001). Although Baxalta pre-
`sents a close question as to disparagement, the facts here
`differ from those of cases finding disclaimer based on the
`specification.
`In Indivior, the asserted patent claimed pharmaceuti-
`cal films with uniform distribution of the active ingredient.
`930 F.3d at 1331. The claims identified “drying” as a pa-
`rameter that contributes to film uniformity. Id. at 1332.
`The specification taught that using conventional drying
`methods, which applied hot air to the top of the film, pro-
`duced nonuniform films. Id. The specification also dis-
`closed controlled drying methods that differed from
`conventional techniques. Id. The district court construed
`the drying limitation to mean “dried without solely employ-
`ing conventional convection air drying from the top” based
`on its conclusion that the patentee disclaimed drying films
`using solely conventional top air drying. Id. at 1336. We
`agreed with the district court’s construction, concluding
`that “the specification repeatedly disparages conventional
`top air drying because such drying does not produce uni-
`form films, the central object of the claimed invention.” Id.
`at 1337. The “specification also provide[d] examples that
`demonstrate[d] the failure of conventional drying methods
`to achieve uniformity.” Id.
`Similarly, we concluded in SciMed that the shared
`specification of the patents-in-suit disclaimed an embodi-
`ment from the scope of the asserted claims. The patents
`were drawn to balloon dilatation catheters containing two
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`passageways, or lumens. 242 F.3d at 1338–39. Two ar-
`rangements of the lumens were practiced in the art: the
`dual lumen configuration and the coaxial lumen configura-
`tion. Id. at 1339. The district court construed the asserted
`claims to be limited to catheters with coaxial lumens, and
`not to read on catheters with dual lumens. Id. We agreed
`with the district court’s construction because the specifica-
`tion unequivocally limited “all embodiments” of the
`claimed invention to a coaxial lumen configuration. Id.
`at 1340, 1343–44. In particular, the specification repeat-
`edly defined “the invention” as catheters having a coaxial
`lumen structure and discussed the disadvantages of prior-
`art catheters having a dual lumen configuration. Id.
`at 1342–44.
`We likewise determined that the patent owner in Gaus
`v. Conair Corp., 363 F.3d 1284 (Fed. Cir. 2004), unequivo-
`cally disclaimed a particular embodiment from its claims’
`scope and therefore could not rely on the doctrine of equiv-
`alents to cover that embodiment. The patent at issue
`claimed a device, such as a hairdryer, comprising “an elec-
`trical operating unit and a pair of spaced-apart electrically
`exposed conductive probe networks.” Id. at 1287. The
`specification “made clear that it is essential to [the] inven-
`tion that the pair of probe networks be separate from the
`voltage-carrying components of the appliance, i.e., the ‘elec-
`trical operating system.’” Id. at 1291. By contrast, the
`specification “criticized prior art in which the protective de-
`vice relied on the fluid coming in contact with the voltage-
`carrying portions of the system.” Id. Thus, we concluded
`that the patent owner “disavowed coverage of devices in
`which the two components are not separate and in which
`the protective cut-off mechanism is not triggered until the
`water reaches the electrical operating system.” Id.
`Each of these cases presented a strong case of dis-
`claimer of a particular feature from the scope of a claim
`because the specification made clear that the invention did
`not include that feature. See Indivior, 930 F.3d at 1337;
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`SciMed, 242 F.3d at 1342–44; Gaus, 363 F.3d at 1291. The
`specification of the ’520 patent disparages random PEGyla-
`tion of FVIII, including random PEGylation targeting
`amines like lysines, but nowhere disparages non-random,
`site-directed amine/lysine PEGylation at the B-domain.
`Thus, we agree with the district court that Bayer did not
`unequivocally disclaim non-random amine/lysine PEGyla-
`tion in the specification.
`
`C
`We turn next to the prosecution history, which can be
`helpful in understanding the proper claim construction.
`We are not persuaded that the prosecution history includes
`a clear and unmistakable surrender of claims directed to
`non-random amine/lysine PEGylation. Nor are we per-
`suaded that Bayer’s statements during prosecution other-
`wise require a claim construction that would exclude such
`conjugates.
`During prosecution of the ’520 patent, the Examiner
`rejected the pending claims as inherently anticipated by a
`patent application filed by Nektar: Bossard.1 On appeal to
`the Patent Trial and Appeal Board, Bayer argued that
`Bossard did not teach the claimed conjugates because
`Bossard’s “alleged showing of B-domain attachment is ran-
`dom PEGylation and does not ensure that attachment oc-
`curs at the B- domain.” J.A. 3507. Bayer also argued that
`its then-rejected claim 58, which ultimately issued as
`claim 1, “excludes compositions of randomly PEGylated
`factor VIII in which some conjugates have PEGylation at
`the B-domain but a large number do not.” Id. Bayer con-
`tinued by stating that:
`The Patent Office . . . relies on passages in Bossard
`that show random PEGylation at any one of nu-
`merous amino acid residues in the 2,332-amino
`
`1 U.S. Patent. Pub. No. 2004/0235734.
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`acid protein that have the disclosed functionality.
`Specifically, the Patent Office asserts that Bossard
`et al. “teach many polymer attachment sites such
`as ‘lysine, cysteine and/or arginine’, ‘amine groups’
`and/or ‘carboxyl groups’ for the site of attachment
`to factor VIII, wherein said many polymer attach-
`ment sites are presented in the B-domain . . . .”
`These types of sites are present in the B-domain,
`but they are also present in many other domains of
`factor VIII. This description does not ensure that
`attachment occurs at the B-domain, and does not
`disclose isolated conjugates with attachment at the
`B-domain.
`J.A. 3507–08 (second ellipsis in original) (citations omitted)
`(emphases added). In response to the Examiner’s Answer
`and specifically the Examiner’s arguments based on
`Bossard, Bayer argued in its reply brief to the Board that:
`Much of the Patent Office’s prior arguments relied
`upon possible conjugation at amines or carboxy
`sites, which are present not only in the B-domain
`but in other domains. Any conjugation with these
`reactive groups is random and does not ensure that
`attachment occurs at the B-domain.
`J.A. 4599 (emphases added).
`Baxalta’s disclaimer arguments based on Bayer’s state-
`ments to the Board have some merit. Ultimately, however,
`we agree with the district court’s view as to how a person
`of ordinary skill in the art would have understood the pros-
`ecution history as a whole. Specifically, we agree with the
`district court that when the “entire passage” from Bayer’s
`reply brief is “read together, it is clear that ‘[a]ny conjuga-
`tion’ refers to the conjugations allegedly disclosed by
`Bossard.” Summ. J. Op., 2018 WL 6727054, at *4. Specif-
`ically, though Bossard “may have taught conjugations at
`various sites on factor VIII, such as amines or carboxy
`sites,” Bayer “argued that the conjugations were not
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`targeted to particular sites” and, thus, “described ‘[a]ny
`conjugation’ in Bossard as random.” Id. As the district
`court reasoned, it “does not follow” that Bayer “defined all
`conjugations with amines or carboxy sites as random.” Id.;
`see also Claim Construction Op., 2018 WL 3212425, at *9
`(“[Bayer] stated that conjugation at amines and carboxy
`sites cannot ensure PEGylation at the B-domain—not that
`conjugation cannot occur at amines and carboxy sites.”).
`We agree with the district court that Bayer distinguished
`the prior art on the ground that it did not teach non-ran-
`dom PEGylation at the B-domain, and that Bayer did not
`clearly and unmistakably disclaim all PEGylation at
`amines and carboxy sites.
`Additional sections of the prosecution history support
`our conclusion. First, the prosecution history reveals that
`Bossard randomly PEGylated at both lysines and cysteines
`on FVIII, which undermines Baxalta’s position that Bayer
`disclaimed the former but not the latter as sites for
`PEGylation. Second, the Board reversed the Examiner’s
`anticipation rejection based on a separate prior-art refer-
`ence, Rostin.2 The Examiner argued that Rostin’s PEG at-
`tached to the lysine in Rostin’s shortened B-domain, and
`thus inherently anticipated Bayer’s claims. The Board dis-
`agreed, holding that Rostin’s PEG did not “necessarily at-
`tach[] to the single lysine located in the [shortened]
`B- domain” because there were many other lysines through-
`out FVIII. J.A. 3589–90. These passages suggest that the
`Examiner and the Board understood that lysine PEGyla-
`tion at the B-domain was within the scope of Bayer’s
`claims.
`Finally, Baxalta’s reliance on the applicants’ state-
`ments during prosecution of the ’520 patent’s European
`
`2 Rostin, J., et al., B-Domain Deleted Recombinant
`Coagulation Factor VIII Modified with Monomethoxy Poly-
`ethylene Glycol, Bioconjugate Chem., 11:387–96 (2000).
`
`

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`Case: 19-2418 Document: 67 Page: 15 Filed: 03/01/2021
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`15
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`counterpart3 is misplaced. To overcome an anticipation re-
`jection, the applicants argued that the asserted prior-art
`reference “teaches random PEGylation at any lysine on the
`FVIII molecule and therefore does not anticipate the pres-
`ently claimed isolated conjugates in which essentially all
`the molecules have a polymer attached at the B-domain.”
`J.A. 7702 (emphasis added). A skilled artisan would not
`read this statement as a clear and unmistakable exclusion
`of non-random lysine PEGylation at the B-domain from the
`asserted ’520 patent claims’ scope. Rather, when read in
`context of the entire response, this statement appears to
`distinguish the process claimed in the European applica-
`tion from the process of random PEGylation using lysine in
`the prior art. Indeed, the applicants argued that “none of
`the references cited by the Examiner anticipate the present
`claims, as they disclose only random modification and not
`specific conjugation at the B-domain.” J.A. 7701–02. More-
`over, the district court correctly noted this court’s admoni-
`tion that “varying legal and procedural requirements for
`obtaining patent protection in foreign countries might ren-
`der consideration of certain types of representations inap-
`propriate for consideration in a claim construction analysis
`of a United States counterpart.”4 Claim Construction Op.,
`
`
`3 Eur. Pat. Appl. No. 11153287.4.
`4 We also consider unpersuasive Baxalta’s reliance
`on Bayer’s statements during prosecution of U.S. Patent
`Application No. 13/748,983, a continuation of the applica-
`tion that issued as the ’520 patent. Similar to the ’520 pa-
`tent specification, Bayer told the Examiner that “[r]andom
`modification of Factor VIII such as by targeting primary
`amines with large polymers such as PEG had been at-
`tempted,” but that this “random approach, however, re-
`sults in a heterogenous product with polymer attachment
`possible at many potential sites.” J.A. 9093. The claims of
`the continuation application recited polymer attachment to
`
`

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`Case: 19-2418 Document: 67 Page: 16 Filed: 03/01/2021
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`16
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
`
`2018 WL 3212425, at *5 (quoting AIA Eng’g Ltd. v. Ma-
`gotteaux Int’l S/A, 657 F.3d 1264, 1279 (Fed. Cir. 2011)).
`Although Baxalta’s challenge presents close questions,
`we conclude that the claim language, specification, and
`prosecution history are more aligned with the district
`court’s construction.
`
`II
`We next consider Baxalta’s challenge to the district
`court’s refusal to define the term “random” in its construc-
`tion of “an isolated polypeptide conjugate” in claim 1. Bax-
`alta contends that the district court’s decision not to
`construe “random” improperly delegated to the jury the
`task of determining claim scope and warrants a new trial
`on infringement. We disagree.
`“When the parties present a fundamental dispute re-
`garding the scope of a claim term, it is the court’s duty to
`resolve it.” O2 Micro Int’l Ltd. v. Beyond Innovation Tech.
`Co., 521 F.3d 1351, 1362 (Fed. Cir. 2008). “This duty re-
`sides with the court because, of course, ‘the ultimate ques-
`tion of construction [is] a legal question.’” Eon Corp. IP
`Holdings v. Silver Spring Networks, Inc., 815 F.3d 1314,
`1318 (Fed. Cir. 2016) (alteration in original) (quoting Teva
`Pharms. USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831, 842
`
`
`FVIII “at only the heavy chain,” not “at the B-domain.”
`J.A. 9091, 9094. Thus, the cited statement is not relevant
`to the construction of the ’520 patent’s different claim term.
`See Microsoft Corp. v. Multi-Tech Sys., Inc., 357 F.3d 1340,
`1349 (Fed. Cir. 2004) (“[T]he prosecution history of one pa-
`tent is relevant to an understanding of the scope of a com-
`mon term in a second patent stemming from the same
`parent application.” (emphasis added)). Even if this state-
`ment were relevant, it still demonstrates, at most, a dis-
`claimer of random PEGylation.
`
`

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`Case: 19-2418 Document: 67 Page: 17 Filed: 03/01/2021
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`BAYER HEALTHCARE LLC v. BAXALTA INC.
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`17
`
`(2015)). We have observed, however, that “a sound claim
`construction need not always purge every shred of ambigu-
`ity.” Id. (quoting Acumed LLC v. Stryker Corp., 483 F.3d
`800, 806 (Fed. Cir. 2007)).
`We conclude that the district court did not violate its
`duty to interpret the claims in declining to provide a de-
`tailed interpretation of the term “random” in its claim con-
`struction instructions to the jury. The district court
`construed the claim term “an isolated polypeptide conju-
`gate” to mean “a polypeptide conjugate where conjugation
`was not random.” The district court resolved the parties’
`controversies as to the meaning of “random.” Specifically,
`the district court addressed and rejected Baxalta’s two ar-
`guments: (1) that “random” conjugation means any conju-
`gation at amines or carboxy sites; and (2) that “random”
`conjugation means all heterogenous conjugation.
`In construing the claim term “an is