Patent Docs

Wisconsin Alumni Research Foundation v. Apple Inc. (Fed. Cir. 2024)

By Kevin E. Noonan --

In a joint appeal of two adverse decisions from the District Court, the Federal Circuit on procedural grounds rejected an appeal from the Wisconsin Alumni Research Foundation ("WARF") in Wisconsin Alumni Research Foundation v. Apple Inc.  The decision was based on the Court's conclusion that WARF was precluded from asserting infringement under the doctrine of equivalents (DOE) after having failed to establish literal infringement and having withdrawn its DOE assertions in an earlier litigation, and also precluded from asserting the same patent on DOE grounds against "next-generation" Apple products similar to ones deemed non-infringing earlier.

The case arose over U.S. Patent No. 5,781,752 directed to "[a] predictor circuit [that] permits advanced execution of instructions . . . [i]n an electronic computer with a single processing unit" (alleged to be infringed by Apple's A7 and A8 processors in one of the decisions at issue and Apple's A9 and A10 processors in the other).  The first decision (WARF I) on appeal (regarding earlier litigation about the A7 and A8 processors in which the District Court found infringement by Apple and the Federal Circuit reversed) is the District's Court's refusal to permit WARF to litigate infringement under DOE that had been withdrawn in the earlier litigation, on the grounds that WARF had affirmatively abandoned that theory of infringement (as explained in the opinion, this abandonment was made in a context where Apple was precluded from introducing evidence at trial of its own patent, No. 9,128,725, regarding similar technology) and that the District Court's construction of the term "particular" ("to be associated with a single load instruction") "foreclosed an equivalent where the prediction could be associated with a group of load instructions" (emphases in opinion) because WARF's DOE theory would "vitiate the claim limitation by rendering meaningless the term "particular."  The District Court (in WARF II) after lifting a stay until resolution of WARF I refused to permit WARF from pursuing infringement of Apple A9 and A10 processors under DOE based on its decision in WARF I, supported by Federal Circuit precedent under Nystrom v. Trex Co., 580 F.3d 1281 (Fed. Cir. 2009), that ruled that "the plaintiff in that case was barred from revisiting a doctrine of equivalents theory of infringement based on waiver of that doctrine in past litigation over materially similar, earlier generation of the same products despite later generations being produced during and after the course of the first litigation."  These appeals followed.

The Federal Circuit affirmed, in an opinion by Judge Prost joined by Judges Taranto and Chen.  As explained in the opinion, WARF argued in its appeal from WARF I that it did not waive its claim of infringement under DOE "generally" with respect to Apple's A7 and A8 processors, and that issue preclusion does not apply in WARF II.  Apple argued that the Kessler doctrine supported the District Court's decision in this regard, see Kessler v. Eldred, 206 U.S. 285 (1907) (the panel agreeing with this argument in its affirmance).

With regard to WARF I and the District Court's waiver determination, the Federal Circuit asserted the preeminence of Federal Circuit law for waiver questions regarding "enforcement of a patent right," citing Harris Corp. v. Ericsson Inc., 417 F.3d 1241, 1250‒51 (Fed. Cir. 2005).  WARF's ultimate position on this question was that the District Court's claim construction of the term "particular" was a change of circumstances that precluded application of waiver in its DOE infringement theory under Exxon Chemical Patents, Inc. v. Lubrizol Corp., 137 F.3d 1475 (Fed. Cir. 1998).  Apple for its part argued that WARF made its own "strategic choice to abandon its [doctrine-of-equivalents] theory in order to prevent Apple from introducing evidence of Apple's own patent during the trial's liability phase," relying in large part upon the Federal Circuit's earlier decision reversing the District Court's finding of literal infringement and the absence in that decision of remand or a new claim construction.

The Federal Circuit agreed with Apple.  Regarding WARF's "changed circumstances" concerning claim construction of the term "particular," the opinion asserts that "[t]he correct inquiry is whether the claim construction changed in a way that would excuse WARF's failure to raise, at the previous trial, the doctrine-of-equivalents theory that it now attempts to reassert in WARF I," concluding that it did not.  The Court held that the interpretation of the term was consistent with Apple's understanding that it should be given its plain and ordinary meaning (supported by its expert's testimony).  In addition, the opinion states that WARF was not prohibited from raising its DOE grounds for infringement at trial despite its assertion of its confidence regarding its literal infringement case.  Nor was the panel convinced that Apple's failure to pursue the narrower construction of the term at trial provided any justification for WARF not earlier pursuing its DOE case.

The Court also held that, "for reasons unrelated to claim construction," WARF had waived its DOE infringement theory.  The basis for this conclusion is that WARF's actions had satisfied the standard under United States v. Olano, 507 U.S. 725, 733 (1993), for "intentional relinquishment or abandonment of a known right" by failing to present substantive arguments before the District Court for infringement under the DOE, citing Boss Control, Inc. v. Bombardier Inc., 410 F.3d 1372, 1380 (Fed. Cir. 2005), and United States v. Hible, 700 F.3d 958, 961 (7th Cir. 2012).  The panel characterized WARF's arguments against waiver as "recharacter[izations]" which the Court found to be contrary to the record.  In the panel's view, WARF "agreed to 'drop doctrine of equivalen[ts] and make no doctrine of equivalents arguments whatsoever at trial'," emphasis in opinion, "in exchange for Apple's agreement not to present its own patent at trial."  This constituted a "relinquishment of a known right" which resulted in the District Court ordering both parties not to present evidence about that Apple patent at trial.  In addition, the Court considered it relevant that both parties retained the "ability to argue their positions on what the plain and ordinary meaning required or allowed."  Under these circumstances, the panel held that while WARF could have pursued its DOE theory at trial that it now asserts, not doing so constituted an abandonment constituting waiver.

Finally, in the WARF I appeal the panel turned to (and rejected) WARF's assertion of Exxon Chemical Patents, Inc. v. Lubrizol Corp.,137 F.3d 1475 (Fed. Cir. 1998), in support of its position.  The Court found WARF's assertion of this precedent, for the proposition that "when the doctrine of equivalents becomes a critical issue only after a new claim construction is adopted on appeal, a plaintiff's prior choice to not present that theory at trial does not constitute abandonment" was overbroad.  In the Court's view, that case involved circumstances where the Federal Circuit held on appeal that the District Court had discretion to consider an unasserted DOE infringement theory because the Federal Circuit had not "dispose[d] of" that infringement theory.  Although "[a]t a bird's eye view" the facts and circumstances in Exxon were similar to those here, the panel found sufficient distinctions to reject WARF's assertion of Exxon in this instance.  In Exxon, the District Court's claim construction "rendered [Plaintiff's] doctrine-of-equivalents theory moot," which was not the case here, and in Exxon "there was no reason for the jury to consider Exxon's doctrine-of-equivalents theory under the uncontested facts."  In this case, "in contrast, there were reasons for WARF to pursue its doctrine-of-equivalents theory—namely, the parties were actively disputing the scope of the plain and ordinary meaning of 'particular' before, during, and after trial," i.e., the question on the meaning of "particular" was not moot.  In addition, here (and not in Exxon) the Court found an affirmative abandonment of its DOE theory of infringement.  Finally, in Exxon, the Federal Circuit "did not grant a per se right to a new trial on the doctrine of equivalents" but provided the District Court with the discretion to do so.

Regarding the WARF II appeal, the Court affirmed based on issue preclusion and the Kessler doctrine.  For the former, the standard applied by the Court is that "(1) the issue sought to be precluded is the same as that involved in a prior action; (2) the issue was actually litigated; (3) the determination of the issue was essential to the final judgment; and (4) the party against whom estoppel is invoked was represented in the prior action," citing Adair v. Sherman, 230 F.3d 890, 893 (7th Cir. 2000); the elements at issue here are limited to the first and second, implicating the question (according to the opinion) of "what is the issue"?  WARF contends the issue in WARF I to be "whether Apple's A7 and A8 processors literally infringe the '752 patent" and in WARF II to be "whether Apple's A9 and A10 processors infringe the '752 patent under the [doctrine of equivalents]."  Apple's contention is the same in both cases to be merely "whether Apple's accused products infringe the '752 patent."  The task the Court appreciates is to determine whether the two pairs of processors -- A7/A8 and A9/A10 -- are "essentially the same" and whether literal and DOE infringement "are part of the same overall issue of infringement."

The opinion notes that "[a]ccused devices are essentially the same where the differences between them are merely colorable or unrelated to the limitations in the claim of the patent," citing ArcelorMittal Atlantique et Lorraine v. AK Steel Corp., 908 F.3d 1267, 1274 (Fed. Cir. 2018).  Here, the District Court held that the pairs of accused infringing processors satisfied this standard, and the Federal Circuit found no clear error in this determination.  The panel dismissed WARF's contentions that there was an issue based on failure of Apple to provide discovery regarding the A9/A10 processors and that there was a "'potential' significant [design] change" in the later-developed A9/A10 processors compared with the A7/A8 processors.  This decision was based on the Court's consideration of further proceedings below wherein both parties made assertions that the two pairs of processors were the same ("not more than colorably different" in Apple's language).  And the only additional discovery WARF wanted was "damaged-related discovery" according to the panel, not technical discovery relevant to the question of substantial sameness at issue here.

The Court next considered the second prong of the test for issue preclusion, "whether the issue is infringement or the separate theories of infringement" and whether the issue litigated in the first action is identical to the one WARF wishes to pursue in the second action under B & B Hardware, Inc. v. Hargis Industries, Inc., 575 U.S. 138, 154 (2015).  Importantly, the panel interpreted the B&B Hardware holding to be that the legal standards applied in both actions were the same, not that the "factors or tests must be identical for issues to be identical."  The Court purports to apply the same analytical approach taken by the B&B Hardware Court, looking at "the statutes, the history, and the Restatement (Second) of Judgments" (i.e., the common law) to make its determination of issue identity.  Here, the statute is the same (35 U.S.C. § 271), as was the historical context for the DOE (Winans v. Denmead, 56 U.S. 330, 344 (1853); see also Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608 (1950), which treated literal and DOE infringement "as a single issue").  Finally, the panel's assessment of the teachings of the Restatement (Second) of Judgments sets forth "several factors" for situations where "there is a lack of total identity between the particular matter presented in the second action and that presented in the first."  These include "substantial overlap in evidence or argument"; whether "new evidence or argument involve application of the same rule of law as that involved in the prior proceeding"; "[c]ould pretrial preparation and discovery relating to the matter presented in the first action reasonably be expected to have embraced the matter sought to be presented in the second?"; and "[h]ow closely related are the claims involved in the two proceedings?"  These rubrics as applied by the Court supported the District Court's determination that issue preclusion should apply to WARF's renewed assertion of infringement under the DOE.  This treatment is also consistent with precedent, according to the opinion, citing Nystrom v. Trex Co., 580 F.3d 1281 (Fed. Cir. 2009) (relied upon by the District Court), and Aspex Eyewear, Inc. v. Marchon Eyewear, Inc., 672 F.3d 1335, 1343 (Fed. Cir. 2012).  The opinion also asserts a policy basis for their decision:

For the foregoing reasons, we are convinced that literal infringement and the doctrine of equivalents are the same issue for issue-preclusion purposes.  To conclude otherwise would allow a patentee to proceed through the entirety of litigation only on a theory of literal infringement and, after losing its case, allow that same party to accuse the same entity of infringing the same patent, accusing the same or essentially the same products, as long as those products were sold after judgment of the first suit.

Finally, the opinion turns to the proper application of the Kessler doctrine in support of the District Court's decision.  The doctrine is specific for patent law, according to the Court, wherein it "fills the gap between [claim and issue] preclusion doctrines . . . allowing an adjudged non-infringer to avoid repeated harassment for continuing its business as usual post-final judgment," citing Brain Life, LLC v. Elekta Inc., 746 F.3d 1045, 1056 (Fed. Cir. 2014).  As applied the right (to sell a non-infringing article after having been absolved of infringement of the claimed invention) "attaches to its product—to a particular thing—as an article of lawful commerce," the panel citing Rubber Tire Wheel Co. v. Goodyear Tire & Rubber Co., 232 U.S. 413, 418 (1914).  Closer to the circumstances in this case (and cited by the Court in support of the District Court's judgment) is SpeedTrack Inc. v. Off. Depot, Inc., 791 F.3d 1317, 1329 (Fed. Cir. 2015), where a plaintiff only asserting literal infringement was precluded under the Kessler doctrine from asserting DOE infringement in a second lawsuit arising after having failed to prevail against the same defendant for accused literal infringement.  As stated in the opinion, "WARF II presents exactly this type of litigation harassment, applied to a second suit against the very same defendant."

These proceedings appear to exonerate Apple from infringement that an earlier jury had decided was worth $506 million (after prejudgment interest).

Wisconsin Alumni Research Foundation v. Apple Inc. (Fed. Cir. 2024)
Panel: Circuit Judges Prost, Taranto, and Chen
Opinion by Circuit Judge Prost

Medtronic, Inc. v. Teleflex Life Sciences Ltd. (Fed. Cir. 2024)

By Kevin E. Noonan --

Last week the Federal Circuit handed down a pair of non-precedential decisions affirming the Patent Trial and Appeal Board (PTAB) in inter partes review (IPR) proceedings.  This post concerns the decision in Medtronic, Inc. v. Teleflex Life Sciences Ltd.

The case arose in two IPR proceedings involving U.S. Patent No. 8,142,413, owned by Teleflex and related to methods for using a coaxial guide catheter in interventional cardiology procedures.  Claims 1, 2, 4, 5, and 7-14 were challenged by Medtronic for being unpatentable for anticipation* or obviousness; claim 1 was considered to be representative by the Court in this appeal:

A method of providing backup support for an interventional cardiology device [ICD]
    for use in the coronary vasculature, the [ICD] being adapted to be passed through a standard guide catheter, the standard guide catheter having continuous lumen extending for a predefined length from a proximal end at a hemostatic valve
    to a distal end adapted to be placed in a branch artery, the continuous lumen of the guide catheter having a circular cross-sectional inner diameter sized such that [ICDs] are insertable into and through the lumen, the method comprising:
        [1.a] inserting the standard guide catheter into a first artery over a guidewire, the standard guide catheter having a distal end;
        [1.b] positioning the distal end of the standard guide catheter in a branch artery that branches off from the first artery;
        [1.c] inserting a flexible tip portion of a coaxial guide catheter defining a tubular structure having a circular cross-section and a length that is shorter than the predefined length of the continuous lumen of the standard guide catheter, into the continuous lumen of the standard guide catheter, and,
        [1.d] further inserting a substantially rigid portion that is proximal of, operably connected to, and more rigid along a longitudinal axis than the flexible tip portion, into the continuous lumen of the standard guide catheter, the substantially rigid portion defining a rail structure without a lumen and having a maximal cross-sectional dimension at a proximal portion that is smaller than the cross-sectional outer diameter of the flexible tip portion and having a length that, when combined with the length of the flexible distal tip portion, defines a total length of the device along the longitudinal axis that is longer than the length of the continuous lumen of the guide catheter;
        [1.e] advancing a distal portion of the flexible tip portion distally beyond the distal end of the standard guide catheter and into the second artery such that the distal portion extends into the second artery and such that at least a portion of the proximal portion of the substantially rigid portion extends proximally through the hemostatic valve;
    and
        [1.f] inserting the [ICD] into and through the continuous lumen of the standard guide catheter alongside of the substantially rigid portion and advancing the [ICD] through and beyond a lumen of the flexible tip portion into contact with or past a lesion in the second artery.

wherein the italicized language in step 1.f is relevant to the issues before the Court.  (The opinion reduces the steps from the complexity of the claim language to the following shorthand regarding the ordered and simplified steps:

1.a: inserting the standard guide catheter;
1.b: positioning the standard guide catheter;
1.c: inserting a coaxial guide catheter;
1.d: inserting a substantially rigid portion;
1.e: advancing the flexible tip portion;
1.f: inserting and advancing the ICD.)

The opinion explains that the claimed method relates to introducing a catheter into coronary arteries through the aorta, and the occasional difficulties arising from "tough lesions"(including stenosis and chronic arterial occlusion) therein which make such introductions difficult and problematic, which are addressed in the claims by using a combination of a guide catheter and a coaxial guide catheter.  The coaxial guide catheter comprises "a tip portion, a reinforced portion, and a substantially rigid portion," with the tip being distal (inserted further into the artery) to the rigid portion.  This arrangement is illustrated by Figs. 8 and 9:

with the following explanation from the '413 patent:

In operation, a guide catheter 56 is inserted into a major blood vessel in the body such as aortic arch 58 over guidewire 64 and the distal end 68 of guide catheter 56 is brought into proximity of ostium 60 of a smaller branch blood vessel, such as coronary artery 62, that it is desired to enter.  Coaxial guide catheter 12, with tapered inner catheter 14, is inserted through guide catheter 56 and over guidewire 64.  Guide catheter 56, guidewire 64, coaxial guide catheter 12, and tapered inner catheter 14 are manipulated to insert tapered inner catheter tip 42 into the ostium 60 of the blood vessel that branches off from the major blood vessel.  The bump tip 22 of coaxial guide catheter 12 is inserted with tapered inner catheter tip 42 well into ostium 60 of coronary artery 62 or other blood vessel until bump tip 22 of coaxial guide catheter 12 achieves a deep-seated position.  Tapered inner catheter 14 is then withdrawn from the lumen of coaxial guide catheter 12.  An interventional cardiology treatment device such as a catheter bearing a stent or a balloon (not shown) is then inserted through the lumen of coaxial guide catheter 12 which remains inside guide catheter 56.

Medtronic challenged these claims in the '413 patent over U.S. Patent No. 7,736,355 (for anticipation) and 7,604,612 (for obviousness, in combination with the '355 patent) in a first IPR and for obviousness over U.S. Patent No. 5,439,445 taken alone or in combination with U.S. Patent Application Publication No. US 2004/0010280.  In rendering its Final Written Decision that the challenged claims were non-obvious over any of these combinations of the asserted prior art, the PTAB construed claim 1 to require that the steps be performed in the recited order.  In both IPRs, the Board further held in its non-obviousness determination that the skilled worker would not have been motivated to combine either set of references.

The Federal Circuit affirmed, in an opinion by Judge Prost, joined by Judges Lourie and Chen.  Regarding the Board's claim construction, the panel affirmed the construction that "inserting the ICD can occur only after advancing the flexible tip portion")(emphasis in opinion); Medtronic advanced a broader interpretation for simultaneous insertion of the ICD and coaxial guide catheter.  The Court reviewed the Board's interpretation of the claim language and support therefor in the specification in arriving at its conclusion.  The relevant portion of the claim language was in 1.e (advancing the flexible tip portion) and 1.f (inserting and advancing the ICD), according to the opinion, which indicates that the tip is  advanced before the ICD if (as the Court affirms) in the proper "in order" recitation of the claimed method steps.  As stated in the opinion, "when the current step of a method claim refers to a previous step using the definite article 'the,' the claim language indicates that the previous step occurs sequentially before the current step," citing Wi-Lan, Inc. v. Apple Inc., 811 F.3d 455, 462 (Fed. Cir. 2016) (although qualifying this principle as not being "an ironclad rule").  This interpretation is further supported by the panel's consideration of the "physical requirements of the substantially rigid portion," in light of the arrangements of the elements (with the tip being "distal" and the rigid portion being "proximal" and that they are "operably connected").  Further recitation of the timing of the insertions also support this interpretation according to the opinion ("the logic of claim 1 suggests that the inserting and advancing the ICD step must occur after advancing the flexible tip portion").  Disclosure in the specification is also consistent with this construction, according to the Court, because it also discloses "an ordered performance of the recited steps in claim 1" as well as the advantages of doing so.

While characterizing Medtronic's construction to the contrary as being "plausible" "in a vacuum," the panel rejects it because Teleflex's construction as adopted by the Board is consistent with the context of the claim language and specification, citing Trs. of Columbia Univ. v. Symantec Corp., 811 F.3d 1359, 1363 (Fed. Cir. 2016).  Medtronic's acquiescence to the requirement for the other steps in the method of claim 1 to be performed in the recited order suggests to the panel that this order should not be interpreted any differently for steps 1.e and 1.f, analogous to the circumstances in Mformation Techs., Inc. v. Rsch. in Motion Ltd., 764 F.3d 1392, 1398 (Fed. Cir. 2014).  And cases that have found disparate step order to be a proper interpretation were cases where such an interpretation was expressly supported by the specification, such as Niazi Licensing Corp. v. St. Jude Med. S.C., Inc., 30 F.4th 1339, 1351–53 (Fed. Cir. 2022), or based on claim differentiation, see Baldwin Graphic Sys., Inc. v. Siebert, Inc., 512 F.3d 1338, 1345 (Fed. Cir. 2008).  Nor were Medtronic's distinctions based on additional recitations in dependent claims 6, 10, and 11 persuasive, the panel stating that the argument "has no support in our reasoning here or the logic and grammar of the claims."

Regarding the Board's finding that the skilled artisan would not have had a reason to combine the '355 and '612 patents, the panel applied the substantial evidence standard of review for what are factual questions supporting the Board's legal determination of non-obviousness.  According to the opinion, the '355 patent discloses an "intravascular foreign matter suction assembly" for removing foreign matter from a blood vessel, whereas the '612 patent discloses emboli protection devices.  The Court rejected Medtronic's assertion of error because, first the Board had expressly considered Medtronic's proposed motivations to combine and its conclusions were supported by substantial evidence; second, the Board compared Medtronic's evidence in favor of a reason to combine the references with Teleflex's contrary evidence and found the latter evidence more persuasive, based in part on expert testimony cited extensively in the Court's opinion; and third, that the Board had not contravened the Supreme Court's decision in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 418–19 (2007), the panel finding that the Board had not improperly applied the "teaching, suggestion, or motivation test" in arriving at its non-obviousness determination.

Turning to the Board's determination that the '445 patent considered alone did not support Medtronic's obviousness challenge, the opinion sets forth the teachings of this patent to be a support catheter (corresponding to the coaxial guide catheter of claim 1) that "protects the fragile balloon of a balloon catheter" (corresponding to the ICD) as that balloon catheter passes through a guide catheter.  The Board determined that the '445 patent had no disclosure of the requirement in claim 1 that the ICD was advanced after advancing the flexible tip portion.  The panel countered Medtronic's assertion of error by noting the "narrow presentation of the evidence" supporting Medtronic's contentions in this regard, including only one paragraph from the '445 patent plus certain expert testimony in support of Medtronic's position.  The Court also found that Medtronic's evidence in support of its position before the Board was wanting, citing Netflix, Inc. v. DivX, LLC, 84 F.4th 1371, 1377 (Fed. Cir. 2023), for the principle that "the Board should also not have to decode a petition to locate additional arguments beyond the ones clearly made."  Also supporting the Board's findings, in the Court's view, was that this argument relied alone on the disclosures of the '445 patent plus the understanding and "ordinary creativity" of the skilled worker, which the Board found insufficient to support an obviousness determination.

Finally, the Court turned to the Board's determination that the combination of the '445 patent and '280 application did not render obvious the challenged claims.  In this regard the panel understood the '280 application to disclose "an emboli protection system that occludes blood flow" by deploying a filter to catch dislodged emboli.  The Board rejected this combination for supporting obviousness because, inter alia, "[the] sealing device [disclosed in the '280 application] is withdrawn before inserting a treatment device like a stent or a balloon because occluding blood flow, which sealing device . . . does, is undesirable," a characterization supported by Teleflex's expert testimony that "occluding blood flow is undesirable, and therefore teaches that the guide seal is deployed only during deployment of the filter and not during the subsequent delivery of [ICDs] such as balloons and stents."  This understanding of the consequences of the combination "undermined what Medtronic['s interpretation] proposed - keeping [the] sealing device . . . in [the] guide catheter . . . during the insertion of a treatment device like [the '445]'s balloon catheter."  The panel rejected Medtronic's argument that the Board had not considered the proposed combination, finding that the Board had done so and come to a contrary conclusion supported by substantial evidence.  The panel held that the Board also properly considered the consequences of the combination of the references and concluded, "in light of the drawbacks of Medtronic's proposed combination" that the skilled worker would not have combined these references as Medtronic contended.

* The Board's decision that the asserted prior art reference did not anticipate the challenged claims was not appealed.

Medtronic, Inc. v. Teleflex Life Sciences Ltd. (Fed. Cir. 2024)
Nonprecedential disposition
Panel: Circuit Judges Lourie, Prost, and Chen
Opinion by Circuit Judge Prost

Malvern Panalytical Inc. v. TA Instruments-Waters LLC (Fed. Cir. 2023)

By Kevin E. Noonan --

One of the characteristics of patent infringement litigation in the aftermath of the Supreme Court's decision in Markman v. Westview Instruments, Inc. (holding that claim construction was a matter of law to be reviewed de novo by the Federal Circuit; but see Teva Pharma. USA, Inc. v. Sandoz, Inc.) was that an inordinate proportion of claim construction decisions were overturned in whole or part.  Those proclivities have been attenuated in the years following the Cybor v. FAS Technologies* opinion, but the Court's recent decision in Malvern Panalytical Inc. v. TA Instruments-Waters LLC is reminiscent of those bygone days of Federal Circuit preeminence.

The case arose in patent infringement litigation when Malvern sued Waters for infringement of U.S. Patent Nos. 8,827,549 and 8,827,549.  The claims of each patent asserted by Malvern were directed to isothermal titration microcalorimeters, used to measure energy absorbed or released during chemical reactions between two compounds.  The claimed microcalorimeters comprise an automatic pipette assembly 220 illustrated in the opinion by this diagram:

The limitation at issue was another component, the pipette guiding mechanism that guides the pipette assembly "between and into at least two positions of operation."  Disclosed are two embodiments, one being "a pipette arm 520 that supports the pipette assembly 220, and an essentially vertical guide rod 530," illustrated by this Figure 5a:

The operation of this structure is described in the specification to be:

"The pipette arm 520 is moveably attached by a sleeve 540 to the guide rod 530, but its motion about the guide rod is restricted by a guide grove 550 in the guide rod 530 and a guide pin 560 that protrudes from the inner surface of the sleeve 540 and which fits into the guide groove 550" wherein the "movement of the pipette assembly 220 in the vertical direction is restricted to the angular positions of the positions of operation," and "rotational movement of the pipette assembly 220 between the angular positions only is permitted when the titration needle 260 is fully retracted from respective positions of operation."

The second embodiment of this claimed element is illustrated by this Figure 6:

In this embodiment, the guide groove in the guide rod 530 is replaced by a coaxial external guide sleeve 610 with corresponding guide paths 620 for the guide arm 520."

Claim 1 of the '549 patent and claim 9 of the '175 patent are set forth as representative:

1.  A micro titration calorimetry system comprising:
    an automatic pipette assembly comprising a titration needle arranged to be inserted into a sample cell for supplying titrant, a syringe for supplying titrant to the titration needle, a stirring paddle for stirring fluid in the sample cell, and a stirring motor for rotating the stirring paddle, and
    a pipette guiding mechanism arranged to restrict the movement of the pipette assembly along safe paths to ensure that the titration needle cannot be damaged during movement thereof between different positions of operation.

9.  A micro titration calorimetry system comprising:
    an automatic pipette assembly comprising a titration needle arranged to be inserted into a sample cell for supplying titrant, a syringe for supplying titrant to the titration needle, a stirring paddle for stirring fluid in the sample cell, and a stirring motor
    for rotating the stirring paddle, and
    a pipette guiding mechanism arranged to guide the pipette assembly between and into at least two positions of operation, wherein a first position of operation is a pipette washing position wherein the titration needle is inserted in a washing apparatus, and a second position of operation is a titration position wherein the titration needle is inserted into the sample cell for calorimetric measurements.

The opinion states as being "relevant to this appeal" prosecution of an unrelated patent, U.S. Patent No. 9,103,782 owned by Malvern.  In that case, applicants were able to overcome an anticipation rejection over U.S. Patent Application Publication No. 2010/0238968 based on common ownership.  Also relevant was a supplemental examination request under 35 U.S.C. § 257 that Malvern filed upon acquisition of the '175 patent.  As part of that effort, Malvern filed an Information Disclosure Statement including references cited against the '782 patent, including the '968 application (although as noted in the opinion Malvern did not characterize the references).  During supplemental examination, the Examiner cited an owner's manual for a prior art microcalorimeter disclosing a manually operated pipette guiding mechanism, which Malvern overcame by affidavit that this manual was the inventors' own work.

Turning to claim construction, the opinion recites the parties' proposed constructions of the term "pipette guiding mechanism," wherein Malvern argued the term meant a "mechanism that guides the pipette assembly," while Waters argued that it should mean a "mechanism that manually guides the pipette assembly"; the District Court adopted Waters' construction.  In ruling on this decision, the District Court characterized the phrase "pipette guiding mechanism" to be a "coined term" that required an examination of the intrinsic evidence to determine the "objective boundaries to the scope of the term," citing Iridescent Networks, Inc. v. AT&T Mobility, LLC, 933 F.3d 1345, 1353 (Fed. Cir. 2019).  In doing so, the District Court relied on statements on the meaning of the term made during prosecution of the '782 patent and that applicants had limited the meaning of the term to manual embodiments.  These arguments were attributed to Malvern as the common assignee of the '782, '549, and '175 patents and because statements made during prosecution of the '782 patent were incorporated into the intrinsic record during supplemental examination.  The parties consented to a stipulated judgment of infringement based on the disputed claim construction and this appeal followed.

The Federal Circuit vacated the stipulated judgment in an opinion by Judge Prost, joined by Judges Hughes and Cunningham.  The panel agreed with Malvern that the term "pipette guiding mechanism" encompassed both manual and automated embodiments based on the intrinsic evidence, specifically the plain meaning of the claims, the specification, and the prosecution history.  Regarding the claim language, the panel considered the plain meaning of the words individually, citing Littelfuse, Inc. v. Mersen USA EP Corp., 29 F.4th 1376, 1381 (Fed. Cir. 2022), and 3M Innovative Props. Co. v. Tredegar Corp., 725 F.3d 1315, 1329 (Fed. Cir. 2013), and found no basis for limiting the pipette guide mechanism to only manual embodiments ("Instead, the broad claim language supports the conclusion that the 'pipette guiding mechanism' encompasses both manual and automatic embodiments.")  Interpreting the claim broadly is consistent, in the panel's view, with how the Court construed the claims in Hill-Rom Services, Inc. v. Stryker Corp., 755 F.3d 1367 (Fed. Cir. 2014), wherein broad claim language supported broad claim interpretation.  And the Court found that the remaining language of the claims similarly supported this interpretation.  According to the opinion, while "[t]he claims clarify and restrict what the guiding mechanism does, . . . they provide no language suggesting the restriction to manual embodiments Waters advocates."

The specification supports this interpretation according to the Court, based on disclosure of two embodiments neither of which is limited to manual pipette guiding mechanisms.  "In fact," the Court says, "the specification states nothing about whether the guiding mechanism is manual or automatic," and cites Hill-Rom Services, Inc. v. Stryker Corp., 755 F.3d 1367, 1373 (Fed. Cir. 2014), for the principle that "[t]here are no magic words that must be used, but to deviate from the plain and ordinary meaning of a claim term to one of skill in the art, the patentee must, with some language, indicate a clear intent to do so in the patent" and, as in Hill-Rom, "there is no such language here."  The Court dismissed Waters' arguments to the contrary because they were based on portions of the disclosure that "say nothing about whether the guiding mechanism is manually or automatically operated."  Nor was the Court persuaded by the fact that other components were described as automatic (and thus not describing the pipette guiding mechanism as being automatic implied the term should be limited to manual embodiments).

Finally, regarding the prosecution history, the Court was not persuaded to Waters' construction by the supplemental examination of the '175 patent, wherein the inventors testified that a manual for a prior art microcalorimeter comprising a manual pipette guide mechanism was their own work and thus not prior art.  Waters argued that this testimony should be interpreted to mean the claimed microcalorimeters of the '175 patent were themselves limited to manual embodiments of the pipette guide mechanisms.  (In a footnote the panel explains that they found the statements to be "too vague or ambiguous to qualify as a disavowal of claim scope.")

Turning to the "coined term" issue which provided one basis for the district court's decision, the opinion notes the District Court's reliance on Indacon, Inc. v. Facebook, Inc., 824 F.3d 1352,  1357–58 (Fed. Cir. 2016), in construing the claims.  While recognizing that their Indacon decision involved the question of construing a claim that did not have an established meaning in the art, the panel maintained that what the District Court had needed to do was "answer the question of what plain and ordinary meaning a term has in the context of a patent," which the District Court here did not do, in the Federal Circuit's opinion.

Finally, the panel considered what weight (if any) to give the prosecution history of the '782 patent.  The Court concluded that the '782 prosecution was not relevant to claim construction of the '175 and '549 patents-in-suit merely because that history had been submitted in an IDS during the supplemental examination of the '175 patent.  The Court relied on its precedent in Goldenberg v. Cytogen, Inc., 373 F.3d 1158, 1167 (Fed. Cir. 2004), that "[i]n the absence of an incorporation into the intrinsic evidence, this court's precedent takes a narrow view on when a related patent or its prosecution history is available to construe the claims of a patent at issue and draws a distinct line between patents that have a familial relationship and those that do not."  And the opinion further asserts that citing the prosecution history in an IDS is at most an admission that "'references in the disclosure may be material to prosecution of the pending claims,' but [] "does not admit materiality," citing Abbott Labs. v. Baxter Pharm. Prods., Inc., 334 F.3d 1274, 1279 (Fed. Cir. 2003) (emphasis added).  The Court concluded here that there was no such admission by Malvern's "bare listing" of the IDS.  And even if considered to be so, the opinion further states that this disclosure was insufficient to amount to disclaimer of automatic pipette guiding mechanisms, because the applicant of the '782 patent had abandoned arguments having to do with scope of claims reciting pipette guiding mechanisms.  Reaching this conclusion was supported by their decision in Ecolab, Inc. v. FMC Corp., 569 F.3d 1335, 1343 (Fed. Cir. 2009), in the Court' view.

For these reasons the panel vacated the District Court's claim construction and remanded, where questions of infringement and claim invalidity will be assessed under the Federal Circuit's construction of the "pipette guiding mechanism" term.  The Court also awarded costs to Malvern.

* In his dissent from this en banc decision upon which de novo review of claim construction by the Federal Circuit was established until partially overturned by the Supreme Court in Teva Pharma v. Sandoz, Judge Rader cited statistics that in 1997, the Federal Circuit reversed 53% of the cases decided (27% reversed completely, 26% reversed in part) and for 246 cases decided by the Federal Circuit after Markman, 141 explicitly reviewed the District Court's claim construction, and reversed, in whole or part, in 54 of these cases (about 38%).  He identified eight problem areas caused by Markman: multiple trials, bias towards summary judgment, new evidence, the "learning curve problem," and a propensity for every decision to be appealed to the CAFC for de novo review.

Malvern Panalytical Inc. v. TA Instruments-Waters LLC (Fed. Cir. 2023)
Panel: Circuit Judges Prosy, Hughes, and Cunningham
Opinion by Circuit Judge Prost

Pacific Biosciences of California, Inc. v. Personal Genomics Taiwan, Inc. (Fed. Cir. 2024)

By Kevin E. Noonan --

The importance of claim construction, and how construing the same term facing a challenge based on different prior art in separate inter partes review proceedings can result in contrary findings on invalidity, was illustrated by the Federal Circuit's decision recently in Pacific Biosciences of California, Inc. v. Personal Genomics Taiwan, Inc.

The case arose in Pacific Bioscience's IPR challenges to different combinations of claims* of U.S. Patent No. 7,767,441, owned by Personal Genomics Taiwan (PGI).  Claim 1, challenged in both IPRs, is representative:

1.  An apparatus for identifying a single biomolecule, comprising:
    a substrate having a light detector; and
    a linker site formed over the light detector, the linker site being treated to affix the biomolecule to the linker site;
    wherein the linker site is proximate to the light detector and is spaced apart from the light detector by a distance of less than or equal to 100 micrometers.

The two instituted IPRs were directed to claims 1, 2, 6, 7, 10–22, 24, and 27–36 ("the '1200 IPR") and claims 1–6, 9, and 43–58 ("the '1163 IPR").  Pacific Biosciences (PacBio) asserted U.S. Patent Application Publication No. 2004/0197793 A1 in the '1200 IPR, on anticipation and obviousness grounds, and International Publication No. WO 2007/045755 A1 in the '1163 IPR, also asserting anticipation or obviousness against the challenged claims.  The Board held in separate Final Written Decisions that PacBio failed to establish invalidity of the challenged claims in the '1200 IPR on either ground, but that the claims challenged in the '1163 IPR were invalid as being anticipated by the '755 published PCT application.  (The opinion notes that the FWD in the '1163 IPR also found invalidity on obviousness grounds that was not at issue in the appeal assessed below.)  As discussed in the Federal Circuit's opinion, both these determinations relied on the Board's construction of the term "identifying a single biomolecule" to have its plain and ordinary meaning encompassing identification of a single molecule and not multiple copies of the same molecule.  This appeal followed by each of the losing parties on each of the IPRs.

The Federal Circuit affirmed the Board's determinations in each IPR, in an opinion by Judge Taranto, joined by Judges Prost and Hughes.  The opinion first addresses the Board's construction of the phrase "identifying a single biomolecule," which was given its plain and ordinary meaning of identifying a single biomolecule and not an amplified or multiplicity of the same biomolecule, or as stated in the opinion "requiring an apparatus capable of ascertaining the identity of one single, individual biomolecule by examining only that biomolecule."  The panel held that the plain and ordinary meaning, both on its face and in the context of the claims and specification supported the Board's construction that as a feature of the claimed apparatus the language recites "(a) ascertaining the identity of a biomolecule, i.e., what that biomolecule is, and (b) doing so by examining just that one biomolecule, not others (even copies)."  The Federal Circuit, reviewing the Board's construction without deference (because it was based solely on intrinsic evidence), nevertheless resorted to two dictionary definitions of "identify" to affirm the Board's construction with regard to the first portion of the definition, and the panel relied on the context of the claim to decide conformity with the second portion.  The "striking feature" the court stated that provided this context was the word "single," the panel stating that "[t]here is no apparent reason for the inclusion of the word 'single' in the phrase except to indicate that the capability required is to identify a molecule with just that one molecule in view."  The Federal Circuit was also persuaded by statements in the specification that the capability to identify singe biomolecules was "critical" to the invention, and that the "single molecule" feature avoided recognized problems in detecting "a population-level signal from an ensemble or cluster of amplified or copied biomolecules."  Finally, regarding claim construction the opinion uses comparisons with the language in other claims in the '441 patent that related to detecting more than one biomolecule to limit claim 1 to identifying a single biomolecule.

Turning to the Board's factual predicates for its decisions on validity (challenged by both appellants), the panel held that the Board's conclusions in each case were supported by substantial evidence.  For the '1200 IPR, the "principal embodiment" disclosed in the cited art was using an assay having a sensitivity that permitted detection of biomolecules in amounts "as low as 0.1 attomoles."  This corresponds to detecting more than 60,000 molecules (according to PacBio's expert), and other portions of the prior art reference recited even higher amounts ("1 amol to 100 amol").  "This evidence," according to the opinion, "provides substantial-evidence support for the Board's finding that [the asserted prior art] does not disclose 'identifying a single biomolecule.'"  For the '1163 IPR, the "critical disclosure" was the capacity of the prior art apparatus to include openings in the detector sufficiently small to detect "individual chromophores" (emphasis in opinion).  In the Court's opinion, this disclosure provided substantial evidence supporting the Board's determination that the prior art was capable of detecting a single biomolecule, because such biomolecules were typically tagged with a single chromophore.  The panel found that the Board had sufficient basis for rejecting a contrary opinion from PGI's expert (that the sensitivity of the prior art detector was no less than 78 biomolecules) that included rebuttal evidence from PacBio that the disclosed improvement in detection provided by the cited prior art ("a factor of 400") could result in a sensitivity improvement permitted single biomolecule detection.  While the panel recognized that PacBio's expert asserted a lower estimate of improved sensitivity ("30 or 40 or 50 times better"), "[w]here the overall evidence reasonably allows the Board's factual finding on a point, we do not 'reweigh the evidence' to reject that finding," citing Regents of the University of California v. Broad Institute, Inc., 903 F.3d 1286, 1294 (Fed. Cir. 2018).  Accordingly, the Federal Circuit affirmed the Board's decisions in these IPRs.

Pacific Biosciences of California, Inc. v. Personal Genomics Taiwan, Inc. (Fed. Cir. 2024)
Panel: Circuit Judges Prost, Taranto, and Hughes
Opinion by Circuit Judge Taranto

* The challenged claims of the '441 patent:

'1200 IPR

'1163 IPR

1. An apparatus for identifying a single biomolecule, comprising: a substrate having a light detector; and a linker site formed over the light detector, the linker site being treated to affix the biomolecule to the linker site; wherein the linker site is proximate to the light detector and is spaced apart from the light detector by a distance of less than or equal to 100 micrometers. 2. The apparatus of claim 1, further comprising a blind sheet formed over the substrate, the blind sheet including a pinhole having a diameter, wherein the linker site is formed proximate to the pinhole. 6. The apparatus of claim 2, further comprising a microlens formed between the substrate and the blind sheet. 7. The apparatus of claim 1, wherein the distance is less than or equal to 25 micrometers. 10. An optical detection system, comprising at least 10,000 apparatuses as recited in claim 1. 11. A method of sequencing a plurality of nucleic acid molecules, the method comprising the steps of: affixing a plurality of nucleic acid molecules to the linker sites of the optical detection system of claim 10; and performing nucleic acid sequencing of the nucleic acid molecules in parallel on the optical detection system. 12. A method of detecting a plurality of biomolecules, the method comprising the steps of: affixing a plurality of biomolecules to the linker sites of the optical detection system of claim 10; and detecting the biomolecules on the optical detection system in parallel. 13. An optical detection system, comprising at least 250,000 apparatuses as recited in claim 1. 14. An optical detection system, comprising at least 2,000,000 apparatuses as recited in claim 1. 15. An optical detection system, comprising at least 10,000,000 apparatuses as recited in claim 1. 16. A method of sequencing a nucleic acid, comprising the steps of: affixing one nucleic acid molecule to the linker site of the apparatus of claim 1; and performing nucleic acid sequencing of the nucleic acid molecule on the apparatus. 17. The method of claim 16, wherein the nucleic acid is affixed to the linker site by binding to a polymerase molecule affixed to the linker site. 18. The method of claim 16, wherein the nucleic acid sequencing comprises the step of adding labeled nucleotides to the apparatus. 19. The method of claim 18, wherein the nucleotides are labeled fluorescently. 20. The method of claim 19, wherein the nucleotides are labeled fluorescently on their terminal phosphate. 21. The method of claim 16, wherein the nucleic acid sequencing is base extension sequencing and includes the step of adding blocked and labeled nucleotides to the apparatus. 22. The method of claim 21, wherein the nucleotides are labeled fluorescently. 24. The method of claim 22, wherein the nucleotides have distinct fluorescent labels and are added simultaneously. 27. The method of claim 16, wherein the sequence of the nucleic acid is unknown. 28. The method of claim 16, wherein the nucleic acid is detected with a label excited by Förster resonance energy transfer (FRET). 29. The method of claim 16, wherein the nucleic acid is detected with a label by time-resolved fluorescence technology. 30. A method of detecting a biomolecule, comprising the steps of: affixing one or more biomolecule to the linker site of the apparatus of claim 1; and detecting the biomolecule on the apparatus. 31. The method of claim 30, wherein the biomolecule comprises a label. 32. The method of claim 31, wherein the label is fluorescent. 33. The method of claim 32, wherein the biomolecule comprises a moiety chosen from a polypeptide, antibody, lipid, vitamin, low molecular weight organic molecule, and polysaccharide. 34. The method of claim 33, wherein the biomolecule is affixed to the linker site of the apparatus by a linking molecule. 35. The method of claim 34, wherein the linking molecule comprises a capture molecule. 36. The method of claim 35, wherein the capture molecule is a protein.

1. An apparatus for identifying a single biomolecule, comprising: a substrate having a light detector; and a linker site formed over the light detector, the linker site being treated to affix the biomolecule to the linker site; wherein the linker site is proximate to the light detector and is spaced apart from the light detector by a distance of less than or equal to 100 micrometers. 2. The apparatus of claim 1, further comprising a blind sheet formed over the substrate, the blind sheet including a pinhole having a diameter, wherein the linker site is formed proximate to the pinhole. 3. The apparatus of claim 2, wherein the pinhole has a diameter of less than or equal to 1,000 nanometers. 4. The apparatus of claim 2, wherein the pinhole has a diameter of less than or equal to 200 nanometers. 5. The apparatus of claim 2, further comprising a filter layer formed between the substrate and the blind sheet. 6. The apparatus of claim 2, further comprising a microlens formed between the substrate and the blind sheet. 9. The apparatus of claim 1, wherein the light detector collects light from the biomolecule within a solid angle, the solid angle being greater than or equal to 0.8 SI steridian. 43. A method of providing biomolecule analysis service, comprising the steps of: providing a sample comprising a biomolecule from a service requester to a service provider; the service requester receiving analytical results from the service provider, wherein the results are produced using the apparatus of claim 1. 44. The method of claim 43, wherein the method is performed for remunerative consideration. 45. The method of claim 44, wherein the service requester and the service provider are mediated by a vendor. 46. The method of claim 43, wherein the analytical results are produced in another country. 47. The method of claim 43, wherein the analytical results are produced in a country other than the United States of America. 48. An apparatus for identifying a single biomolecule, comprising: a substrate having a light detector; a linker site formed over the light detector, the linker site being treated to affix the biomolecule to the linker site; and an excitation light source formed over the substrate; wherein the linker site is proximate to the light detector and is spaced apart from the light detector by a distance of less than or equal to 100 micrometers. 49. The apparatus of claim 48, wherein the excitation light source includes a light emitting layer, the light emitting layer emitting excitation light to the linker site along a horizontal direction parallel to a surface of the light detector. 50. The apparatus of claim 49, further comprising a filter layer formed between the substrate and the light emitting layer. 51. The apparatus of claim 48, wherein the excitation light source is chosen from a light emitting diode (LED), an organic light emitting diode (OLED), a polymer light emitting diode (PLED), and a laser diode (LD). 52. The apparatus of claim 48, wherein the excitation light source provides excitation light of a first wavelength range not overlapping with a second wavelength range of light emitted from the biomolecule. 53. An apparatus for identifying a single biomolecule, comprising: a substrate having a light detector; and a linker site formed over the light detector, the linker site being treated to affix the biomolecule to the linker site; wherein the light detector collects light emitted from the biomolecule within a solid angle of greater than or equal to 0.8 SI steridian. 54. An apparatus for identifying a single biomolecule, comprising: a substrate having a light detector; a linker site formed over the light detector, the linker site being treated to affix the biomolecule to it; and an excitation light source formed over the substrate; wherein the light detector collects light emitted from the biomolecule within a solid angle of greater than or equal to 0.8 SI steridian. 55. A method for manufacturing an apparatus for identifying a single biomolecule, comprising: forming a light detector and a control circuit on a substrate; forming a blind sheet having a pinhole over the substrate; and forming a linker site over the light detector and proximate to the pinhole, the linker site being treated to affix the biomolecule to the linker site, wherein the linker site is proximate to the light detector and is spaced apart from the light detector by a distance of less than or equal to 100 micrometers. 56. The method of claim 55, further comprising forming a filter layer between the substrate and the blind sheet. 57. The method of claim 56, wherein forming the blind sheet comprises: forming an opaque layer on the filter layer; forming a photoresist layer on the opaque layer; patterning the photoresist layer to expose a portion of the opaque layer; etching the opaque layer using the patterned photoresist layer as a mask until the filter layer is exposed; and removing the photoresist layer. 58. The method of claim 57, wherein the opaque layer comprises metal.

H. Lundbeck A/S v. Lupin Ltd. (Fed. Cir. 2023)*

By Kevin E. Noonan --

The provisions of U.S. regulatory law regarding FDA approval for less than all the indications for which an innovator drug was approved under 21 U.S.C. § 355(j)(2)(A)(viii) (the so-called "skinny label) has in the recent past raised something of a kerfuffle before the Federal Circuit (see "GlaxoSmithKline LLC v. Teva Pharmaceuticals USA (Fed. Cir. 2022)").  In contrast, the patency of skinny label approvals under the patent statute was affirmed by the Federal Circuit in a December 7th decision in H. Lundbeck A/S v. Lupin Ltd.

The case arose in ANDA litigation in which Lundbeck and assorted plaintiffs asserted U.S. Patent No. 9,278,096, directed to use of the antidepressant vortioxetine (Trintellix®) for treating patients who discontinued or reduced treatment with other antidepressants due to "sexually related adverse effects," and U.S. Patent No. 9,125,910 for treating patients with vortioxetine for cognitive impairment against all defendants, and U.S. Patent No. 9,101,626, directed to methods for making vortioxetine against defendant Lupin.  Takeda is the NDA holder for Trintellix® and the opinion notes that two patents not in suit, U.S. Patent No. 7,144,884 and 8,476,297 (on the drug compound) expire on June 17, 2026 and expired on October 2, 2022, respectively.  In contrast, the patents in suit expire on March 21, 2032 (the '096 patent) and June 15, 2027 (the '910 patent).  Defendants filed "Paragraph III" ANDAs on the '884 and '297 patents, which ANDAs are limited to treatment of major depressive disorder; this indication is not claimed in the '096 or '910 patents-in-suit.

Claims 1 and 7 of the '096 patent are representative of claims for treating depression without or with reduced adverse sexual side effects with vortioxetine:

1.  A method for the treatment of a disease selected from the group consisting of depression, anxiety, abuse and chronic pain, comprising the administration of a therapeutically effective amount of [vortioxetine] or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein said patient has previously received medication or is still receiving medication for the treatment of said disease, the medication is ceased or reduced or has to be ceased or reduced due to sexually related adverse events, and the medication is selected from the group consisting of selective serotonin reuptake inhibitors, selective noradrenaline reuptake inhibitors, noradrenaline/serotonin reuptake inhibitors, and tri-cyclics.

6.  The method according to claim 1, wherein Compound I or a pharmaceutically acceptable salt thereof is administered to the patient in unit doses of about 1–50 mg.

7.  The method according to claim 6, wherein the patient is administered between about 1 and 20 mg per day of the hydrobromic acid salt of Compound I orally.

Claims 1, 3, and 6 of the '096 patent are representative of claims for treating cognitive impairment with vortioxetine:

1.  A method of treating cognitive impairment involving decline in speed of processing, executive function, attention, or verbal learning and memory in a patient diagnosed with depression, the method comprising administering a therapeutically effective amount of [vortioxetine] or a pharmaceutically acceptable salt thereof to the patient, wherein . . . the method alleviates a symptom or complication of the cognitive impairment or delays the progression of the cognitive impairment.

3.  The method of claim 1, wherein the depression is major depressive disorder.

6.  The method of claim 3, wherein the method comprises administering a hydrobromide salt of [vortioxetine] to the patient.

Plaintiffs asserted induced or contributory infringement against defendants, asking the District Court for an injunction until the '096 and '910 patents expired.  The District Court held that defendants' ANDAs "neither induced infringement of nor contributorily infringed" the '096 nor '910 patents, and denied the injunction.  Plaintiffs appealed this judgment.

In addition, plaintiffs asserted the '626 patent against defendant Lupin, the opinion stating that claims 1 and 11 were representative; claim 1 recites:

1.  A process for the preparation of [vortioxetine] or a pharmaceutically salt thereof, the process comprising reacting compound II . . ., with a compound of formula III . . ., and a compound [IV] . . ., in the presence of a solvent, a base and a palladium catalyst consisting of a palladium source and a phosphine ligand at a temperature between 60° C. and 130° C.

The District Court construed the claims consistent with plaintiffs' interpretation of the word "reacting" and held Lupin's method of producing vortioxetine would infringe.  Lupin cross-appealed this judgment.

The Federal Circuit affirmed, in an opinion by Judge Dyk joined by Judges Prost and Hughes.  Plaintiffs argued that an infringement action under § 271(e)(2)(A) "creates a separate cause of action that does not require a showing of direct, induced, or contributory infringement by the ANDA filer"; in other words filing an ANDA by itself is an act of infringement.  In the context of this lawsuit, Plaintiffs also asserted that "it makes no difference that the drug is proposed to be sold for a use not covered by the '096 and '910 patents because the drug could be prescribed for those patented uses."  The panel rejected this argument, stating that "'the use . . . claimed in a patent' under section 271(e)(2)(A) must be the use for which an applicant is seeking marketing approval" under their case law.**  The opinion cites Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365 (Fed. Cir. 2003), in support of this determination, the opinion stating that how a drug was used was a necessary factor in determining infringement.  This is because otherwise the NDA holder for a particular drug could extend its exclusivity "by regularly filing a new patent application claiming a narrow method of use not covered by its NDA, [which] would confer substantial additional rights on pioneer drug patent owners that Congress quite clearly did not intend to confer," citing Warner Lambert.  Despite the possibility of off-label use, that possibility does not override the basis in § 271(e)(2)(A) to be limited to preventing an ANDA filer from approval for uses subject to patent protection; here, defendants do not seek approval for the uses claimed in the '096 and '910 patents.  Such uses do not raise infringement liability under §§ 271(a), 271(b), or 271(c) and § 271(e)(2)(A) does not create infringement liability independently of these statutory bases for finding infringement, according to the Federal Circuit.

Turning to the District Court's findings that defendants' ANDAs did not constitute infringement of claim 7 under § 271(b), the opinion cites that "instructions may not merely describe an infringing mode; they must 'evidence intent to encourage infringement,'" citing Takeda Pharms. U.S.A., Inc. v. West-Ward Pharm. Corp., 785 F.3d 625, 630–31 (Fed. Cir. 2015).  Plaintiffs' sole evidence for inducing infringement liability was the FDA-approved label, which does not induce infringement of the asserted claims of the '096 patent because it is limited to the indication for treating major depressive disorder (which indication the opinion notes predates the '096 patent).  The opinion expressly distinguishes this situation with that in GlaxoSmithKline LLC v. Teva Pharmaceuticals USA, Inc., 7 F.4th 1320, 1333 (Fed. Cir. 2021), where there was evidence of the existence of advertising or promotional activities and materials that encouraged infringement inter alia by off-label use stratagems.  The panel reiterates their interpretation of § 271(e)(2)(A) that "a patentee can[not] bar the sale of a drug for a use covered only by patents that will have expired simply by securing a new patent for an additional, narrower use," citing Warner-Lambert.  Further, the Court opined:

[W]e do not see how, in the normal course, a label required to market the drug for a use covered by expired patents could demonstrate the required specific intent to encourage infringement of new patents covering different uses.

The panel notes that there may be circumstances (related to safety, for example) where FDA requires a new patented method of use to be included on the label due to such safety concerns, citing for example AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060– 61 (Fed. Cir. 2010) (instructions to lower a dose for safety reasons); Vanda Pharms. Inc. v. West-Ward Pharms. Int'l Ltd., 887 F.3d 1117, 1131 (Fed. Cir. 2018) (requiring a test and adjustment of drug dose accordingly); and Eli Lilly & Co. v. Teva Parenteral Medicines, Inc., 845 F.3d 1357, 1365, 1368–69 (Fed. Cir. 2017) (taking a supplement to reduce "potentially life-threatening toxicities").  That is not the case here according to the opinion.  Rather, these defendants had properly under the statute "carved out" the indications encompassed by the '096 patent claims, and accordingly the Court held that "[t]he district court correctly determined that, under these circumstances and consistent with our cases," the proposed ANDA labels "will not encourage, recommend, or promote an infringing use."

The opinion concludes its considerations of the induced infringement issue by rejecting plaintiffs' argument that physicians could prescribe the approved drug based on their own "background knowledge together with information in the carved-out label," stating that "mere knowledge of possible infringement by others does not amount to inducement; specific intent and action to induce infringement must be proven," again based on the Warner=Lambert opinion.  Also rejected was plaintiffs' assertion of error by the District Court in "ignoring the lower doses recited in the '096 patent claims, while at the same time arguing with regard to claim validity that the skilled worker would have recognized the lower incidence of adverse sexual events that resulted at any of the approved dosages, the panel stating that "Plaintiffs cannot now fault the district court for crediting their own argument."

With regard to contributory infringement, the panel likewise rejected plaintiffs' arguments, here because there is no liability for contributory infringement for selling an article that is "suitable for substantial noninfringing use" under the statute, 35 U.S.C. § 271(c).  The opinion states that the District Court properly found that vortioxetine had such substantial noninfringing uses over the claims of the '096 patent, for example, by prescribing the drug to "patients with no prior treatment, patients with prior treatment other than with the drugs referenced in the '096 patent, and in cases where the prior antidepressant was ceased or reduced for reasons other than sexually related adverse events (for example, due to poor efficacy)."  Similarly for the '910 patent, substantial noninfringing uses found sufficient to avoid contributory infringement include "prescription for treating MDD, prescription to patients without cognitive impairment, and prescription for purposes unrelated to cognition."  And plaintiffs' assertion that these uses may infringe other Lundbeck patents is not relevant, according to the Court, because the determination under § 271(c) relates and is limited to substantial noninfringing uses of the asserted patents.

In Lupin's cross-appeal regarding the District Court's infringement determination of the '626 patent, the Court found no basis to adopt Lupin's narrow interpretation of the term "reacting" based on the term's plain meaning and rejected Lupin's assertion of the prosecution history for its contrary construction.  The Court found no error by the District Court either for its claim construction nor its infringement determination.

The Court apportioned costs to the defendants in plaintiffs' appeal of the judgment of non-infringement of the '096 and '910 patents and to plaintiffs in defendant Lupin's appeal of the District Court's judgment of infringement of the '626 patent.

Lundbeck A/S v. Lupin Ltd. (Fed. Cir. 2023)
Panel: Circuit Judges Dyk, Prost, and Hughes
Opinion by Circuit Judge Dyk

* The caption in full reads as follows:

H. LUNDBECK A/S, TAKEDA PHARMACEUTICAL COMPANY LIMITED, TAKEDA PHARMACEUTICALS U.S.A., INC., TAKEDA PHARMACEUTICALS INTERNATIONAL AG, TAKEDA PHARMACEUTICALS AMERICA, INC., Plaintiffs-Appellants

v.

LUPIN LTD., LUPIN PHARMACEUTICALS, INC., MACLEODS PHARMA USA, INC., MACLEODS PHARMACEUTICALS LTD., SANDOZ INC., SIGMAPHARM LABORATORIES, LLC, ZYDUS PHARMACEUTICALS (USA) INC., ALEMBIC GLOBAL HOLDING S.A., ALEMBIC PHARMACEUTICALS INC., ALEMBIC PHARMACEUTICALS LIMITED, CADILA HEALTHCARELTD., LEK PHARMACEUTICLS D.D.

** Defendants contended that this argument was waived by it not having been asserted at the district court.

Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2023)

By Kevin E. Noonan --

Proper construction of claim limitations reciting the chemical property of pH (which denotes the concentration of hydrogen ions in a solution as an indication of acidity) has arisen several times in district court and Federal Circuit opinions, perhaps the most notable being in Warner-Jenkinson v. Hilton Davis Chemical (1997), which revitalized the doctrine of equivalents.  The issue arose recently before the Federal Circuit in Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc., with the Court vacating and remanding the District Court's claim construction for failure to consider extrinsic evidence.  The opinion illustrates the difficulties posed and considerations considered by the Court when addressing claim constriction for terms comprising pH.

The case arose in ANDA litigation related to Actelion's Flolan® (epoprostenol) product, used for treatment of cardiovascular disease.  As described in the opinion, the compound is unstable in water and prepared by Actelion as a freeze-dried or lyophilized power for reconstitution in commercially available IV fluids prior to use (intravenous administration to a patient) without needing refrigeration (sold by Actelion as Veletri®).  The patents-in-suit were U.S. Patent Nos. 8,318,802 and 8,598,227, with claim 11 of the '802 patent being set forth as representative:

11.  A lyophilisate formed from a bulk solution comprising:
    (a) epoprostenol or a salt thereof;
    (b) arginine;
    (c) sodium hydroxide; and
    (d) water,
    wherein the bulk solution has a pH of 13 or higher, and wherein said lyophilisate is capable of being reconstituted for intravenous administration with an intravenous fluid.

(wherein the italicized limitation was at issue in the case).  The opinion also notes that the inventor's discovery that epoprostenol formulations "in the presence of an alkalinizing agent, and high pH (>11) is very stable compared to Flolan" was unexpected.  Litigation ensued when Mylan sent Actelion a Paragraph IV letter under 21 U.S.C. § 355(j)(2)(A)(vii)(IV), with Actelion asserting claims 1, 6, 8, 10, 11, 16, 18, 20, and 22 of the '802 patent and claims 1–3, 8, 10, 12, 14, 16, 18–22, and 24–42 of the '227 patent under 35 U.S.C. § 271(e)(2).

Both parties argued that the pH limitation should be construed by its ordinary and customary meaning but differed as to what that meaning was.  Actelion argued that the term "a pH of 13 or higher" should be construed as giving the acidity value of the solution as an order of magnitude subject to conventional rounding rules, wherein the term would include a pH of 12.5 (which would be rounded up to 13).  Mylan, on the other hand, argued that the term cannot properly be construed to include any pH value less than 13 and if interpreted as a range must be between pH 12.995 and 13.004 based on the concept of significant figures (or digits) in view of the logarithmic nature of pH values.  Both parties asserted chemical textbooks to support their claim construction arguments.

The District Court declined the parties' invitations to consider the proffered textbook definitions as extrinsic evidence and construed the limitation according to Actelion's plain meaning definition based solely on the intrinsic evidence.  According to the District Court, the plain meaning of a numerical value included two significant figures and thus "a pH of 13" would ordinarily encompass values from 12.5 to 13.4.  Neither the specification nor the prosecution history contained any disclosure that would implicate any "increased degree of precision" according to the District Court.  The parties stipulated infringement in favor of Actelion, the District Court entered judgment, and this appeal followed.

The Federal Circuit vacated the judgment and remanded to the District Court for further claim construction in light of extrinsic evidence, in an opinion by Judge Stoll joined by Judges Reyna and Stark.  After reciting the standard of review (de novo for claim construction relying solely on intrinsic evidence, clear error for claim construction relying on extrinsic evidence, and de novo on the "ultimate interpretation of the claim"), the panel turned to the "narrow question" of the proper meaning of "a pH of 13" in the context of the '802 and 227 patents.  Put simply, the Court found the intrinsic evidence to be "equivocal" and the extrinsic evidence asserted by the parties and not considered by the District Court to be "highly relevant to how a person of ordinary skill would understand the [disputed claim] language."  The opinion then reviewed the conventional sources of claim construction (the "plain and ordinary meaning" of the claim language, the specification and the prosecution history) to explicate their conclusion that the intrinsic evidence was equivocal.  Regarding the "plain and ordinary meaning" of the claim language, the panel disagreed with Mylan's construction involving the range from pH 13 to the upper range of pH 14, stating that such cases are "not of great significance to our analysis here" and "there is no blanket rule that ranges, or specifically open-ended ranges, must foreclose rounding."  The opinion also notes that while the claims lack any conventional "approximation language" such as "about" the panel did not agree with Mylan's argument that as a consequence the term "a pH of 13" must be construed to mean exactly pH 13.  The opinion states that this absence of approximation language is not dispositive and that the Court is not interested in promulgating a "bright line rule" on this question (and the opinion notes the panel finds both parties' arguments to be "equally plausible").

Regarding the specification, the panel finds the language therein to be inconsistent.  In some sections the pH of the "bulk solution" are described as being "adjusted to about 12.5-13.5, most preferably 13" (and also distinguished pH 12.5 from pH 13 and the range of pH 12.5-13.5 from pH 13) while elsewhere pH 13 is described as "pH 13.0," which would indicate a more restricted scope for this limitation.  Mylan argued (unsuccessfully before the district court as well as the panel) that these disclosures precluded the claim term "pH 13" from encompassing a range and in particular pH 12.5.  These arguments, and Actelion's responses, convinced the panel that "the specification supplies the same clarity as to the desired level of precision as muddied water" and thus could not be relied upon to provide intrinsic evidence of the meaning of pH 13 in the claims.  Further, while the significance of the pH term was in the stability of the drug compound epoprostenol in the formulation, the opinion finds no evidence in the specification that stability was tested in the range of pH 12-pH 13 upon which the claim term could be definitively construed.

And regarding the prosecution history, the Court considered several amendments to the claims involving the pH limitation, and statements by the Examiner that evidence regarding formulations at pH 12 did not distinguish over the prior art but those at pH 13 did so (the amendments resulting in the claim language in the granted patents were included in the Reasons for Allowance).

Under these circumstances the panel decided that:

We find that this case is one where the proper claim construction cannot be reached without the aid of extrinsic evidence, and that the district court should have considered, at minimum, the textbook excerpts offered and addressed by the parties.

This decision was supported by Supreme Court precedent (Teva Pharms. USA, Inc. v. Sandoz, Inc., 574 U.S. 318, 331 (2015), and Federal Circuit case law (Pickholtz v. Rainbow Techs., Inc., 284 F.3d 1365, 1372–73 (Fed. Cir. 2002)) cited in the opinion.

Accordingly, the panel decided to vacate and remand, because:

It is not for this court to make those findings [regarding extrinsic evidence] in the first instance.  We decline to decide, for example, how many significant figures "a pH of 13" has or what it would mean for a number—either for a pH value or for the concentration of hydrogen ions—to have zero significant figures.  Instead, we leave those and other relevant factual questions that might arise based on the extrinsic evidence, including the three textbooks, for the district court to address in the first instance.

Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2023)
Panel:  Circuit Judges Reyna, Stoll, and Stark
Opinion by Circuit Judge Stoll

Medytox, Inc. v. Galderma S.A. (Fed. Cir. 2023)

By Kevin E. Noonan --

It is not surprising that the Federal Circuit has taken the opportunity to apply the Supreme Court's recent precedent in Amgen v. Sanofi regarding the sufficiency of disclosure needed to satisfy the statutory enablement requirement under 35 US.C. § 112(a).  After all, the decision is a rare affirmance of Federal Circuit decision by the Supreme Court, and the legal rationale set forth is consistent with recent enablement jurisprudence developed by the Federal Circuit over recent years (see "Wyeth & Cordis Corp. v. Abbott Laboratories", "Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc.", and "Idenix Pharmaceuticals LLC v. Gilead Sciences Inc.").  But the decision, in Medytox, Inc. v. Galderma S.A., is itself significant because it adopts the analytical framework that the Patent and Trademark Office and district courts can be expected to follow going forward, for better or worse.

The case arose in a post-grant review (PGR) proceeding against U.S. Patent No. 10,143,728 before the Patent Trial and Appeal Board pursuant to 35 U.S.C. § 321 et seq. and brought by Galderma et al.  The challenged claims were directed towards "the use of an animal-protein-free botulinum toxin composition that exhibits a longer lasting effect in the patient compared to an animal protein-containing botulinum toxin composition," which encompasses a Medytox product designated MT10109L in the opinion.  Substitute claim 19 was set forth in the opinion as representative:

A method for treating glabellar lines a condition in a patient in need thereof, comprising:
    locally administering a first treatment of therapeutically effective amount of a botulinum toxin composition comprising a serotype A botulinum toxin in an amount present in about 20 units of MT10109L, a first stabilizer comprising a polysorbate, and at least one additional stabilizer, and that does not comprise an animal-derived product or recombinant human albumin;
    locally administering a second treatment of the botulinum toxin composition at a time interval after the first treatment;
    wherein said time interval is the length of effect of the serotype A botulinum toxin composition as determined by physician's live assessment at maximum frown;
    wherein said botulinum toxin composition has a greater length of effect compared to about 20 units of BOTOX®, when whereby the botulinum toxin composition exhibits a longer lasting effect in the patient when compared to treatment of the same condition with a botulinum toxin composition that contains an animal-derived product or recombinant human albumin dosed at a comparable amount and administered in the same manner for the treatment of glabellar lines and to the same locations(s) as that of the botulinum toxin composition; and
    wherein said greater length of effect is determined by physician's live assessment at maximum frown and requires a responder rate at 16 weeks after the first treatment of 50% or greater that does not comprise an animal-derived product or recombinant human albumin, wherein the condition is selected from the group consisting of glabellar lines, marionette lines, brow furrows, lateral canthal lines, and any combination thereof.

(wherein the claim is presented with limitations removed from the substitute claim indicate by strikethrough and those added by underlining).  The compositions were disclosed in earlier applications incorporated by reference; this application newly provides in support of these method claims the results of two clinical trials that compared botulinum toxin stabilized with human serum albumin and animal-protein-free botulinum toxin composition.  One of these was results of a Phase III clinical trial making the relevant comparison between BOTOX® and the claimed MT10109L product (showing not surprisingly "significant improvement" with the Medytox product), and results of a Phase II clinical trial comparing the two products (showing consistent improved results with the Medytox product).

The PTAB instituted a PGR against granted claims 1-10 of the '728 patent and Medytox filed a motion to amend by cancelling claims 1-10 and substituting claims 11-18.  Medytox also requested the Board to issue a Preliminary Guidance (as part of the PTO's Pilot Program regarding amendment practice in PGRs and other post-grant review proceedings) relating to the likelihood that the motion met statutory and regulatory requirements.  Galderma opposed the motion to amend on new matter grounds, and the PTAB issued a Preliminary Guidance that "Medytox had not shown a reasonable likelihood that it satisfied the statutory and regulatory requirements under 35 U.S.C. § 326(d) and 37 C.F.R. § 42.221(a)."  But the Guidance also contained the caveat that the Board would not be bound by this Guidance in its Final Written Decision, which would depend on the full record before the Board at the end of the proceedings.  In response, Medytox moved to cancel original claim 6 and substitute the remaining claims with new claims 19-27, which motion Galderma also opposed.

The Board issued its FWD and cancelled original claims 1-5 and 7-10.  On the merits of the remaining claims at issue, the Board construed the term "responder rate" with regard to Galderma's (a range of 50-100%) and Medytox's (a minimum threshold of 50%) constructions, ultimately deciding that the responder rate limitation had an upper limit of 100% (a construction that differed from the one in the Preliminary Guidance).  The Board also found that Medytox's substitute claims introduced new matter in the responder rate limitation and thus failed to meet the requirements for its revised motion to amend.  The Board accordingly found that the proposed substitute claims were invalid for failure to satisfy the written description requirement (a finding not addressed by the Federal Circuit on appeal, in view of its other grounds for affirming the Board).  On the Board's decision that the substitute claims were also not enabled, the Board applied the factors set forth in In re Wands and, based in part on expert testimony, found that the full scope of the claims was not enabled because the specification would not have enabled the skilled worker to achieve a responder rate higher than 62% without undue experimentation.  All claims in the '728 patent were thus cancelled or replacement with substitute claims precluded by their being invalid.  This appeal followed.

The Federal Circuit affirmed, in an opinion by Judge Reyna joined by Judges Dyk and Stark.  The opinion first discussed claim construction, the panel holding that the Board properly construed the "responder rate" limitation to be a range (Galderma also arguing that Medytox on appeal for the first time contended that its construction relied on intrinsic evidence in the specification rather than extrinsic, expert testimony understandably, in light of the substantial evidence standard of review of Board decisions based on factual determinations such as expert testimony).  The Court did not address Galderma's underlying forfeiture argument, asserting instead that the parties did not dispute that the "responder rate" limitation had an "inherent" upper limit of 100% and that "there appears to be no substantive difference in the claim construction proposed by the parties for the responder rate limitation," the Federal Circuit affirming the Board's construction on that basis.

Turning to enablement, the Federal Circuit held that the Board had properly found the '728 specification did not satisfy the enablement requirement of § 112(a).  The panel rejected Medytox's argument that "the specification does not need to include a working example of 'every possible embodiment to enable the full scope of the claims,'" citing (somewhat anachronistically) Bayer Healthcare LLC v. Baxalta Inc., 989 F.3d 964, 982 (Fed Cir. 2021), and Medytox's reliance on expert testimony that there would require no undue experimentation because it was "routine to clinically confirm" whether a composition met the duration limitation (a "greater length of effect").  Galderma had argued that Medytox was required "to provide a clinical study for each formulation because clinical trials are not routine for 'determining whether pharmaceutical compositions fall within the scope of a patent claim.'"  The Federal Circuit agreed, cabining the extent of its agreement by asserting that "our caselaw may not require disclosure of every possible working example of responder rates" but noting that here the specification disclosed "at most three examples of responder rates above 50% at 16 weeks."  While citing earlier caselaw, including Wyeth & Cordis Corp. v. Abbott Lab'ys, 720 F.3d 1380, 1385–86 (Fed. Cir. 2013), and MagSil Corp. v. Hitachi Global Storage Techs., Inc., 687 F.3d 1377, 1381 (Fed. Cir. 2012), the panel based its decision on the Supreme Court rubric recently set forth in Amgen v. Sanofi that "[t]he more one claims, the more one must enable."  The opinion expressly states the basis for its analytical reasoning as also sounding in Amgen, that:

Though a specification need not always "describe with particularity how to make and use every single embodiment within a claimed class," it must nevertheless "enable the full scope of the invention as defined by its claims," for example by "disclosing [a] general quality" of the class that may "reliably enable a person skilled in the art to make and use all of what is claimed."

Applying these principles, the Federal Circuit affirmed the Board's non-enablement decision based on substantial evidence that that "the arguments and evidence were insufficient to demonstrate enablement to a skilled artisan because said artisan 'would not have been able to achieve' responder rates higher than the limited examples provided in the specification."

Procedurally, Medytox argued that the Board erred in changing its claim construction in the FWD from the construction in the Preliminary Guidance as a violation of the Administrative Procedures Act (APA) as being arbitrary and capricious under 5 U.S.C. § 706(2)(A).  Medytox's arguments focused on the Board's purported failure to consider intrinsic evidence and this had resulted in "inconsistent conclusions on a nearly identical record" [that] render[ed] its decision arbitrary and capricious," citing BASF Corp. v. Enthone, Inc., 749 F. App'x 978, 985 (Fed. Cir. 2018), and Robert Bosch, LLC v. Iancu, 778 F. App'x 871, 875 (Fed. Cir. 2019).  The Federal Circuit's assessment is in line with the arguments put forth by the Solicitor General on behalf of the Patent Office, that the Preliminary Guidance is preliminary and any contrary conclusions the Board may arrive at in its FWD is due to the further development of the record during the proceedings, something the Federal Circuit has held is an obligation falling on the Board, citing In re Magnum Oil Tools Int'l, Ltd., 829 F.3d 1364, 1377 (Fed. Cir. 2016).  Here, the panel held that the Board "provided a reasoned analysis for its ultimate claim construction" and consequently that the decision to change its construction of the claims with regard to the responder rate limitation was not arbitrary and capricious.

Finally, Medytox argued that the Board's decision and the way it was arrived at denied them due process and was contrary to the APA.  The Federal Circuit considered the public notice in the Federal Register that the Pilot Program would product a preliminary guidance, and that the "initial" and non-binding nature thereof was evident.  Reviewing the procedural steps below the Court held that there was no irregularities or denial of due process.  Some caution is provided by the Court on the limits of the application of these processes, however:

To be sure, the agency must inform the parties on procedures relevant to its practices, like the Pilot Program, and must respect the boundaries imposed by the APA.  There must be structural integrity to the program in ensuring that the patent owners who have requested such guidance be given an opportunity to be heard and due process.

But on the record before the panel the Court held that these requirements were met.

However this first foray into applying the Supreme Court's latest imperative on how patent law will be interpreted, it is hard to say whether it bodes well.  Perhaps it is the inevitable consequence of a generalist Court steeped in considerations of the "totality of the circumstances" as the reviewing court for an inferior court charged by Congress with interpreting and harmonizing a specific area of the law.  Perhaps it has something to do with that Court spending more than a decade objecting to precedent from the inferior court that attempted to provide such harmony by developing a jurisprudence that could be applied reliably to diverse circumstances and technologies with a minimum of uncertainty.  But as with so much of the Court's "guidance" (to both the courts, the Patent Office, and the patenting public) this one on enablement seems more attuned to the Potter Steward method of legal analysis, wherein "you know it when you see it."  In addition to being anathema to the vision Congress and the early judges had in establishing the Federal Circuit, its difficulty in putting the rubrics (such as they may be) into practice has created disharmony in other areas of the law (see, e.g., "An Analytic Approach to Patent Eligibility") that may now be the fate of enablement law.  The one thread to be grasped in the Court's Amgen decision is the possibility of "[a] general quality" of the class that may "reliably enable a person skilled in the art to make and use all of what is claimed."  Whether this thread can be woven into a fabric through which enablement law can be applied consistently of course remains to be seen.

Medytox, Inc. v. Galderma S.A. (Fed. Cir. 2023)
Panel: Circuit Judges Dyk, Reyna, and Stark
Opinion by Circuit Judge Reyna

American National Manufacturing v. Sleep Number Corp. (Fed. Cir. 2022)

By Kevin E. Noonan --

The Federal Circuit today affirmed determinations by the Patent Trial and Appeal Board (PTAB) in an inter partes review in American National Manufacturing v. Sleep Number Corp., in an opinion by Judge Cunningham.  The opinion was not Judge Cunningham's first Federal Circuit opinion but it is likely to be her shortest, coming in at 862 words (including footnotes).*

The patent, U.S. Patent No. 5,904,172, was challenged over claims 2, 4, 6, 12, 16, 20, 22, and 24.  The opinion sets forth no representative claim but claim 2 will suffice to understand the Court's decision here:

2.  An improved valve enclosure assembly for use with an air inflatable mattress having at least one air bladder inflated by compressed air, a pump fluidly coupled to the at least one air bladder for providing compressed air thereto, and a processor for providing commands to the improved valve enclosure assembly during an inflate/deflate cycle, the improved valve enclosure assembly being fluidly coupled intermediate the pump and the at least one air bladder for controlling the inflation of the at least one air bladder, comprising:
    an enclosure defining a substantially fluidly sealed air chamber and having at least one air inlet to the air chamber being fluidly coupled to the pump, a plurality of guides and stops being disposed within the enclosure for correctly positioning components within the enclosure; and
    pressure monitor means being operably coupled to the processor and being in fluid communication with the at least one bladder for continuously monitoring the pressure in the at least one bladder.

The Board found in favor of ANM's challenge that claim 16** was anticipated but held ANM had not shown by a preponderance of the evidence that the cited art rendered the other claims obvious.  Without much preamble or any recitation of the PTAB's reasoning, the opinion, in which Judges Stoll and Schall joined, begins by rejecting ANM's claim construction arguments, specifically with regard to the term "substantially fluidly sealed" to mean "largely but not wholly sealed," saying that the alternative constructions proposed by the parties (presumably, both of them) were not supported by the intrinsic evidence.  The opinion also rejected ANM's arguments concerning the Board's construction of the term "guides" to mean "structures that position a component, prior to fastening, by directing the component into place," and the term "stops" to mean "structures that position a component, prior to fastening, by arresting travel into the enclosure" on the same basis, that the proposed alternative constructions would add additional, unsupported temporal limitations or enforce an "order of the steps."  The panel found the Board's claim construction to be supported by substantial evidence, referring to specific interpretations of the claims in view of certain specific prior art and reciting with approval the distinctions that convinced the Board that the claims were non-obvious.  The Federal Circuit similarly rejected SNC's challenges to the Board's decision finding claim 16 anticipated by U.S. Patent No. 5,044,029 (the basis for this determination being left to the reader).

The panel "decline[d] to reach" SNC's arguments challenging the Board's construction of the term "pressure monitor means . . . for monitoring" as recited in claims 12 and 16, because SNC had prevailed before the Board for claim 12 and SNC had not asserted its construction before the Board for claim 16.

And with that, the Federal Circuit affirmed, with the coda that each party would bear its own costs.

This case, which is non-precedential, could have been disposed of under Rule 36 but having the Court set out its reasoning parsimoniously has the advantage that the parties and the patent bar and community can better understand the arguments and reasoning the Court found persuasive.

*For comparison, this post which aims for pithy exposition of the Court's decisions is 861 words in length.

**Claim 16:

16.  An improved valve enclosure assembly for use with an air inflatable mattress having at least one air bladder inflated by compressed air, a pump fluidly coupled to the at least one air bladder for providing compressed air thereto, and a processor for providing commands to the improved valve enclosure assembly during an inflate/deflate cycle, the improved valve enclosure assembly being fluidly coupled intermediate the pump and the at least one air bladder for controlling the inflation of the at least one air bladder, comprising:
    an enclosure defining a substantially fluidly sealed air chamber and having at least one air inlet to the air chamber being fluidly coupled to the pump, the enclosure being formed of an enclosure portion and a rear cover portion, a flexible seal being compressively interposed between the enclosure portion and a rear cover portion to effect a substantially fluid tight seal therebetween;
    at least one valve operably coupled to the enclosure being in selective fluid communication with the air chamber and being in fluid communication with the at least one air bladder for selectively fluidly coupling the air chamber to at least one air bladder; and
    pressure monitor means being operably coupled to the processor and being in fluid communication with the at least one valve for monitoring the pressure in the at least one bladder.

American National Manufacturing v. Sleep Number Corp. (Fed. Cir. 2022)
Nonprecedential disposition
Panel: Circuit Judges Stoll, Schall, and Cunningham
Opinion by Circuit Judge Cunningham

University of Massachusetts v. L'Oreal S.A. (Fed. Cir. 2022)

By Kevin E. Noonan --

In reviewing (and reversing) the District Court's claim construction in University of Massachusetts v. L'Oreal S.A., the Federal Circuit availed itself of both the disclosure in the specification and the prosecution history to construe a limitation in a wherein clause, based on its determination that the term did not have a plain meaning and thus other indicia of what the claim term at issue meant should be considered.  The Court also reviewed the District Court's favorable consideration of L'Oreal S.A.'s motion to dismiss on jurisdictional grounds, vacating this determination as an abuse of discretion for failure to grant the University jurisdictional discovery.

The issue arose in the University's lawsuit for patent infringement against L'Oreal S.A. and L'Oreal USA, Inc. over U.S. Patent Nos. 6,423,327 and 6,645,513; the opinion sets forth claim 1 of the '327 patent as representative:

1.  A method for enhancing the condition of unbroken skin of a mammal by reducing one or more of wrinkling, roughness, dryness, or laxity of the skin, without increasing dermal cell proliferation, the method comprising topically applying to the skin a composition comprising a concentration of adenosine in an amount effective to enhance the condition of the skin without increasing dermal cell proliferation, wherein the adenosine concentration applied to the dermal cells is 10^-4 M to 10^-7.

(Where the District Court's construction of the italicized language was the basis for its determination that the claims were invalid for being indefinite.)

While the District Court proceedings were ongoing, L'Oreal USA petitioned the Patent Trial and Appeal Board (PTAB) for institution of inter partes review, which the Board denied.  However, the Board in making its assessment of the institution petition construed the "wherein" clause of claim 1 of the '327 patent to mean the concentration of adenosine at the dermal cells (located underneath the skin surface) rather that the concentration at the skin surface (which comprises the epidermis) (the opinion noting that under 35 U.S.C. § 314(d) these determinations were "final and unappealable").  The District Court also construed the wherein clause to have this meaning without overt construction, holding that the clause was given its "plain and ordinary meaning without the need for further construction."

In applying this construction to the question of invalidity under 35 U.S.C. § 112(b), the District Court granted summary judgment for L'Oreal USA that the claim was indefinite in reciting the limitation "topically applying to the skin a composition comprising a concentration of adenosine in an amount effective to enhance the condition of the skin without increasing dermal cell proliferation" because of the perceived distinctness between the amount of adenosine (directly) applied to the epidermis and the amount (indirectly) applied to the dermal cells and the resulting concentration that is sufficient to both enhance the condition of the skin while not increasing dermal cell proliferation.

The Federal Circuit reversed the District Court's claim construction and vacated summary judgment of indefiniteness in an opinion by Judge Taranto, joined by Judges Mayer and Prost.  The University argued with regard to the claim construction issue that the concentration recited in the wherein clause should be construed to mean the amount of adenosine in the dermis after it has entered the dermal layer, i.e., "the number of moles of adenosine divided by the volume (liters) of the dermis itself."  The Federal Circuit disagreed, holding that the District Court had erred in its construction and vacating and remanding for proceedings based on the Court's construction as set forth in this opinion.  (Review was de novo, because  the District Court relied only upon intrinsic evidence.)  The Court's analysis began with its determination that the meaning of the concentration language in the wherein clause, viewed in the context of the claim as a whole, was not plain and even less plain under the University's construction of it.  The opinion notes that the clause recites adenosine concentration administered to the dermal cells, while the preceding clause relating to skin enhancement recited applying the adenosine-containing composition to the skin (the epidermis). While the way the claim is written with regard of the term "applied" suggested to the panel (as it did to the Board and District Court) a difference in meaning, that is not enough according to the opinion.  The panel recognized that "[t]he same [composition] can be applied directly to one object [(the skin)] and indirectly to the other [(the dermis)]."  Under the Federal Circuit's construction, the concentration of adenosine referenced in the two portions of the claim are the same concentration, which the opinion states is consistent with the language of the dependent claims as well.  The concentration referenced in the skin-enhancement clause refers to the concentration in the composition before it is applied to the skin, which is the same concentration referenced in the wherein clause in the Court's opinion, contrary to the University's proposed construction.  According to the opinion, the University's construction would have the concentration recited in the wherein clause refer to something that does not exist until the composition is applied (and the adenosine absorbed into the skin and the dermal layer).  But if that construction was followed, the wherein clause (in the Court's view) would need to be rewritten to recite "wherein the adenosine permeating to the dermal layer results in a concentration of adenosine in the dermal layer of 10^-4 M to 10^-7 M."  The need for these linguistic gymnastics was enough for the panel to hold that the claim language at issue had no plain meaning and that resort to the specification and prosecution history was in order.

In its review of the disclosure in the specification, the many recitations of the concentration of adenosine in the disclosed composition did not set forth this concentration after penetration into the dermal layer; instead they all disclose concentrations before the composition is applied to the skin.  The opinion states that "[t]his is significant evidence that the wherein clause is best read to refer to the concentration of adenosine in the composition applied to the surface of the skin," referencing Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (en banc); VirnetX, Inc. v. Cisco Systems, Inc., 767 F.3d 1308, 1318 (Fed. Cir. 2014); and Netcraft Corp. v. eBay, Inc., 549 F.3d 1394, 1397–98 (Fed. Cir. 2008).  And there is no disclosure of measuring adenosine concentration in the dermis or the need to do so.

But it is in the prosecution history that the Court found the most persuasive evidence for its construction that the concentration recited in the claims should be construed as the adenosine concentration in the composition before application to the skin.  The Court first looked to the claims as filed, which did not recite the wherein clause present in the claims as granted (that limitation was recited in a dependent claim, but without any mention of dermal cells).  The applicants amended the claim to overcome prior art, and in incorporating the adenosine concentration limitation into the independent claim changed the wording to what was recited in claim 1 of the '327 patent.  However, in their response containing this amendment, the applicants maintained that "[t]his amendment would add no new matter, as it merely includes a range of concentrations of adenosine recited in dependent claims" (emphasis in opinion).  In this response the applicants further distinguished two other prior art references based on concentration of adenosine in the composition before being applied to the skin (as the opinion states, "with no suggestion of a difference in location of concentration measurement").  And the examiner's comments in the reasons for allowance, both in the '327 patent and the '513 patent, contained the statement that the "[i]nstant claims are directed to a method of enhancing the condition of unbroken skin . . . where the method comprises administering adenosine at a concentration of 10^-4 M to 10^-7 M, to the skin" (emphasis in opinion).  In view of this prosecution history, the Federal Circuit held that "the wherein clause's reference to the recited concentrations being 'applied to the dermal cells' be read as referring to concentrations of the composition applied to the skin's surface."  The construction the University advanced before the District Court and on appeal was inconsistent with this history according to the opinion, and "cannot fairly be squared with the understanding that both [the University] and the examiner expressed during prosecution, and on which skilled artisans are entitled to rely," this latter phrase perhaps providing the impetus for the Court's decision.

And in remaining unpersuaded by the University's attempts to distinguish the prosecution history, the Court refused to credit statements in the prosecution history made in response to the examiner's reasons for allowance, which merely recited the claim language and asserted that the applicants did not concede that the examiner's reasons were the only reasons the claims should be allowed (illustrating the futility in believing that such statements would be persuasive in actions to enforce the patent).

The Federal Circuit, applying its construction concluded that the District Court's finding that the claims were indefinite "must be vacated and . . . remanded for the district court to conduct any further proceedings that are necessary" (the panel refusing L'Oreal's suggestion that it enter a judgment of non-infringement directly).

Regarding the jurisdictional question, the District Court adopted a magistrate judge's recommendation that the Court grant L'Oreal S.A.'s motion to dismiss under Federal Rule of Civil Procedure 12(b)(2) without permitting jurisdictional discovery to the University.  The Federal Circuit disapproved of that action, holding that under Third Circuit law it was an abuse of discretion.  The basis for this holding was that "at the very least" jurisdictional discovery was appropriate under Eurofins Pharma US Holdings v. BioAlliance Pharma SA, 623 F.3d 147, 157 (3d Cir. 2010).  The University had "made more than clearly frivolous, bare allegations that L'Oréal S.A. was subject to personal jurisdiction," these allegations including that "L'Oréal S.A. introduced the accused products into the stream of commerce" and that L'Oreal USA was "L'Oréal S.A.'s agent in certain potentially relevant respects."  There was also evidence that L'Oreal S.A. had performed product research on adenosine-containing compositions for treating skin and may have licensed the technology to L'Oreal USA.  Also telling for the panel was that "L'Oréal S.A. did not specifically deny allegations that it developed and licensed the relevant technology to L'Oréal USA" but instead had rather weakly asserted that it had not "directly developed" any of the skincare products at issue in the lawsuit.  The Federal Circuit held that because "this evidence raises the possibility that discovery might have uncovered the requisite contacts under our precedent" (emphasis in opinion), it vacated the District Court's jurisdictional determinations and held that on remand the University was entitled to jurisdictional discovery before the District Court came to and jurisdictional conclusions.

University of Massachusetts v. L'Oreal S.A. (Fed. Cir. 2022)
Panel: Circuit Judges Prost, Mayer, and Taranto
Opinion by Circuit Judge Taranto

Amgen Inc. v. Vidal (Fed. Cir. 2022)

By Donald Zuhn –-

Earlier today, the Federal Circuit reversed the Final Written Decision, and reconsideration of that decision, by the U.S. Patent and Trademark Office Patent Trial and Appeal Board, which determined that claims 1-24 of U.S. Patent No. 8,952,138 were unpatentable under 35 U.S.C. § 103(a).

The '138 patent is directed to methods for refolding proteins at high concentrations using a controlled reduction-oxidation (redox) reaction.  Claim 1, the lone independent claim, is set forth below:

1.  A method of refolding a protein expressed in a non-mammalian expression system and present in a volume at a concentration of 2.0 g/L or greater comprising:
    (a) contacting the protein with a refold buffer comprising a redox component comprising a final thiol-pair ratio having a range of 0.001 to 100 and a redox buffer strength of 2 mM or greater and one or more of:
        (i) a denaturant;
        (ii) an aggregation suppressor; and
        (iii) a protein stabilizer; to form a refold mixture;
    (b) incubating the refold mixture; and
    (c) isolating the protein from the refold mixture.

This appeal arose from a challenge of the '138 patent in an inter partes review by Petitioners Apotex Inc. and Apotex Corp.  In its Final Written Decision, the Board construed the term "final thiol-pair ratio" as meaning "the relationship of the reduced and oxidized redox species used in the redox component of the refold buffer as defined by the [following] equation":
                    [reductant]²
                    [oxidant]

Based on this construction, the Board determined that the Petitioners had demonstrated that claims 1-24 were unpatentable over U.S. Patent Publication No. 2007/0238860 in view of Hevehan and Clark, 54 Biotechnology & Bioengineering 221 (1997).  Amgen appealed the Board's construction and determination of unpatentability, Apotex declined to participate in the appeal, and the USPTO intervened to defend the Board's decision.

On appeal, Amgen argued that the Board misconstrued the term "final thiol-pair ratio" because the claim "language makes clear that the redox component is a distinct volume from the refold buffer, and it is that redox component [rather than the refold buffer] that comprises the claimed 'final thiol-pair ratio'" (emphasis in Appellant's brief).  According to the opinion, the Office "assume[d] that the only way to give meaning to the word 'final' in 'final thiol-pair ratio' and make sense of the '138 patent's claims and specification is to understand 'final thiol-pair ratio' in the context of the ultimate solution—i.e., the refold mixture—rather than specific ingredients therein—e.g., the redox component."

The panel agreed with Amgen, noting that "[a] straightforward reading of the claim language indicates that the 'final thiol-pair ratio' is an attribute of the redox component."  The opinion also notes that the '138 patent specification distinguishes between the terms:

• "final thiol-pair ratio" -- "In various embodiments the redox component has a final thiol-pair ratio" (emphasis in opinion);
• "buffer thiol-pair ratio" – "As used herein, the term 'buffer thiol-pair ratio' is defined by the relationship of the reduced and oxidized redox species used in the refold buffer . . ." (emphasis in opinion); and
• "system thiol-pair ratio" -- "The buffer thiol-pair ratio is, however, only one component in determining the total system thiol-pair ratio in the total reaction" (emphasis in opinion).

In view of the claim language and disclosure in the specification, the panel determined that:

[T]he specification clearly and exclusively describes "final thiol-part ratio" as an attribute of the redox component.  If claim 1 covered a [thiol-pair ratio] calculated in the refold buffer—as the Board construed and analyzed claim 1—claim 1 would have recited a "buffer thiol-pair ratio" rather than "final thiol-pair ratio."

The opinion states that "[t]he Board's construction, which treats the claimed 'final thiol-pair ratio' as an attribute of the redox component in the refold buffer rather than of the redox component independent of the refold buffer, is inconsistent with the plain language of claim 1 and the specification and is therefore unreasonably broad" (emphasis in opinion).  The panel, therefore, held that the Board misconstrued the term "final thiol-pair ratio," and reversed the Board's decision, holding that Apotex had failed to demonstrate that claims 1-24 of the '138 patent were unpatentable under § 103(a).

Amgen Inc. v. Vidal (Fed. Cir. 2022)
Nonprecedential disposition
Panel: Circuit Judges Chen, Schall, and Stoll
Opinion by Circuit Judge Chen

Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH, and Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021)

By Kevin E. Noonan --

The Federal Circuit issued three decisions on Monday relating to Eli Lilly & Co's. challenge in separate inter partes review proceedings on obviousness grounds of nine patents licensed by Teva Pharmaceuticals Int'l, with disparate results.

The patents were related to humanized monoclonal antibodies immunologically specific for calcitonin gene-related peptide (CGRP), for treatment of "all forms of vascular headache, including migraines"; each party marketed a product for this purpose (Teva's AJOVY® and Lilly's Emgality®).  The appeals clustered separate but related IPR proceedings that the Board had combined for oral argument.  In the first of these (as considered here), Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH, Lilly appealed the Board's decision that it had failed to show that challenged claims 1, 3, 4, 8–17, 19, 20, and 24–31 of U.S. Patent No. 8,586,045, claims 1–18 of U.S. Patent No. 9,884,907, and claims 1–18 of U.S. Patent No. 9,884,908 were obvious.  Representative claims from each patent are:

The '045 patent:

1.  A method for reducing incidence of or treating at least one vasomotor symptom in an individual, comprising administering to the individual an effective amount of an anti-CGRP antagonist anti-body, wherein said anti-CGRP antagonist antibody is a human monoclonal antibody or a humanized monoclonal antibody.

The '907 patent:

1.  A method for treating headache in an individual, comprising:
    administering to the individual an effective amount of a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody, comprising:
    two human IgG heavy chains, each heavy chain comprising three complementarity determining regions (CDRs) and four framework regions, wherein portions of the two heavy chains together form an Fc region; and
    two light chains, each light chain comprising three CDRs and four framework regions;
    wherein the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO:15 or SEQ ID NO:43.

The '908 patent:

1.  A method for treating headache in an individual, comprising:
    administering to the individual an effective amount of a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody, comprising:
    two human IgG heavy chains, each heavy chain comprising three complementarity determining regions (CDRs) and four framework regions, wherein portions of the two heavy chains together form an Fc region; and
    two light chains, each light chain comprising three CDRs and four framework regions;
    wherein the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO:15 or SEQ ID NO: 43, and wherein the antibody binds to the CGRP with a binding affinity (KD) of about 10 nM or less as measured by surface plasmon resonance at 37^o C.

Lilly asserted three prior art references in support of its obviousness challenge:

• Olesen et al., "Calcitonin Gene-Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine," N. ENG. J. MED. 350: 1104–10 (2004), which taught treatment of migraine with CGRP receptor antagonist.

• Tan et al., "Calcitonin gene-related peptide as an endogenous vasodilator: immunoblockade studies in vivo with an anti-calcitonin gene-related peptide monoclonal antibody and its Fab' fragment," 89 CLINICAL SCI. 6: 565–73 (1995), which taught using full-length anti-CGRP mAb to block CGRP binding to its receptor in rats.

• U.S. Patent No. 6,180,370, which is a general reference teaching use of "recombinant DNA and monoclonal antibody technologies for developing novel therapeutic agents."

The Board rendered its decision that Lilly failed to show the challenged claims were obvious over this art.  This decision depended in part of its claim construction wherein the preambles of each of the challenged claims constituted a "statement of intended purpose" and were limiting to that extent, which thus raised in Lilly the burden of showing that the skilled worker would have had a reasonable expectation of success in achieving this intended purpose.  In a bit of circular reasoning, the Board construed the claim term "effective amount" to be the amount that would achieve this preamble purpose of a beneficial result but not a clinical result (i.e., of treating migraine).

The Board found the cited art taught each and every one of the limitations recited in the claims, and the skilled artisan would have been motivated to combine the teachings in the cited art and that safety concerns would not have deterred, discouraged, or taught away from pursuing" the invention.  But Lilly failed to show a reasonable expectation of success in the Board's opinion, including that the blood-brain barrier "raised uncertainty, unpredictability, and skepticism in using full-length anti-CGRP antibodies" therapeutically.  This was enough to defeat obviousness for these method claims, which the panel stated was consistent with Honeywell International Inc. v. Mexichem Amanco Holdings S.A. DE C.V., 865 F.3d 1348, 1356 (Fed. Cir. 2017), and were analogous to Novartis Pharmaceuticals Corp. v. West-Ward Pharmaceuticals International Ltd., 923 F.3d 1051 (Fed. Cir. 2019).

The Federal Circuit affirmed in a decision (as all three decisions were) by Judge Lourie joined by Judges Bryson and O'Malley.  On appeal, Lilly raised two arguments.  First, that the Board's claim construction was in error for interpreting the preambles to require a beneficial result that was related to the construction of "effective amount."  Second, Lilly argued the Board's standard for reasonable expectation of success was improperly high.

With regard to claim construction, the panel agreed with Teva that the Board properly construed the preambles to be limiting.  Specific to the facts in each case, as it must be under Storage Tech. Corp. v. Cisco Sys., Inc., 329 F.3d 823, 831 (Fed. Cir. 2003), here the panel held that in this case, the claims were directed to methods for achieving a particular purpose, i.e., "treating or reducing the incidence of vasomotor symptoms, and the method comprises a single step of administering an effective amount of a composition, namely, a humanized anti-CGRP antagonist antibody."  The panel recognized the contrast between method claims such as these and composition of matter or apparatus claims, which are directed to what the claimed invention is rather than what it does, citing Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1468 (Fed. Cir 1990); Cochlear Bone Anchored Solutions AB v. Oticon Med. AB, 958 F.3d 1348, 1355 (Fed. Cir. 2020); Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003); and Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333 (Fed. Cir. 2003).  The Board's construction with regard to the limiting nature of the preambles satisfied the "essence of the claimed invention" requirement and thus was proper.  Recitation of the affirmative limitation of an "effective amount" raised the question of an "effective amount" to do what according to the opinion, which is to achieve the purpose recited in the preamble (the opinion calls this "the only metric by which one practicing the claim could determine whether the amount administered is an 'effective amount'").  The specification defined this amount to be "an amount sufficient to effect beneficial or desired results" and further the specification contained "extensive discussions of such treatment in every section of the patent[]," according to the opinion.  Under these circumstances the panel held that the preamble thus gives "life and meaning" to the claimed methods and is thus properly construed to be limiting.  And the panel further recognized that the preamble also provides antecedent basis for reciting "an individual" in the affirmative limitations recited in the claim, distinguishing Cochlear because that was an apparatus claim and method claims were at issue here.

Turning to reasonable expectation of success, the panel pointed out that the Board's finding of sufficient motivation to combine does not necessarily satisfy the reasonable expectation of success standard, citing Procter & Gamble Co. v. Teva Pharms. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009), and in particular Novartis Pharmaceuticals Corp. v. West-Ward Pharmaceuticals International Ltd., 923 F.3d 1051 (Fed. Cir. 2019).  The Court found the claims here to be analogous to those in WestWard, where despite there being motivation to combine, the biology involved was sufficiently uncertain and unpredictable for there to be no reasonable expectation of success.  Because the limitations in the preamble were properly construed by the Board to require successful methods of treatment, these limitations informed the expectation of success argument as to what is expected and what constitutes success according to the Court.

This understanding by the Board as supported by definition in specification according to the opinion:

As is understood by those skilled in the art, individuals may vary in terms of their response to treatment, and, as such, for example, a "method of reducing incidence of headache in an individual" reflects administering the anti-CGRP antagonist antibody based on a reasonable expectation that such administration may likely cause such a reduction in incidence in that particular individual.

The expectation was not based on a requirement for clinical data (which Lilly argued) and not supported by "isolated, out-of-context statements plucked from dozens of pages of the Board's factual findings" by Lilly.  As in the Court's decision in Sanofi v. Watson Labs. Inc., 875 F.3d 636, 647 (Fed. Cir. 2017), the panel "decline[d] to infer a demand for data from the Board's observation that references did not include those data."  The substantial evidence standard merited the panel's deference to the Board's conclusion that Lilly had not shown a reasonable expectation of success for the challenged method claims.

The Court also rejected Lilly's challenge of error based on considerations of the blood-brain barrier and whether there was uncertainty regarding the capacity for the claimed antibodies to traverse this natural barrier.  Lilly argued that the prior art showed some evidence for migraine relief in the absence of crossing the blood-brain barrier, and thus that any basis by the Board for finding no reasonable expectation of success on this basis as error.  The Court focused on the uncertainty of whether the antibody therapeutic used in the claimed method would actually cross the blood-brain barrier or would need to do so to provide a beneficial effect.  The Court held that Lilly bore the burden of establishing a reasonable expectation of success which under the facts considered by the Board it did not do.

The second appeal, Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., was directed to the Board's finding that claims to anti-CGRP monoclonal antibodies were obvious.  The claims challenged by Lilly in these IPRs were claims 1–7 and 15–20 of U.S. Patent No. 9,340,614, claims 1–6 and 14–19 of U.S. Patent No. 9,266,951, and claims 1–5 of U.S. Patent No. 9,890,210.  The following claims are representative:

The '614 patent:

1.  A human or humanized monoclonal anti-CGRP antagonist antibody that preferentially binds to human α-CGRP as compared to amylin.

The '951 patent:

1.  A human or humanized monoclonal anti-CGRP antagonist antibody that (1) binds human α-CGRP and (2) inhibits cyclic adenosine monophosphate (cAMP) activation in cells.

The '210 patent:

1.  A humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist anti-body, comprising:
    two human IgG heavy chains, each heavy chain comprising three complementarity determining regions (CDRs) and four framework regions, wherein portions of the two heavy chains together form an Fc region; and
    two light chains, each light chain comprising three CDRs and four framework regions;
    wherein the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO:15 or SEQ ID NO:43.

Lilly asserted these prior art references in support of its obviousness challenge in these IPRs:

• Tan et al., "Calcitonin gene-related peptide as an endogenous vasodilator: immunoblockade studies in vivo with an anti-calcitonin gene-related peptide monoclonal antibody and its Fab' fragment," 89 CLINICAL SCI. 6: 565–73 (1995), which taught using full-length anti-CGRP mAb to block CGRP binding to its receptor in rats.

• Wimalawansa, "Calcitonin Gene-Related Pep-tide and its Receptors: Molecular Genetics, Physiology, Pathophysiology, and Therapeutic Potentials," 17 ENDOCRINE REVIEWS 5: 533–85 (1996), which is a review article regarding CGRP, its structure and effects, as well as possible uses for agonists and antagonists.

• U.S. Patent No. 6,180,370, which is a general reference teaching use of "recombinant DNA and monoclonal antibody technologies for developing novel therapeutic agents."

The Board found the skilled worker would have both a reason to combine these teachings to achieve the claimed invention and have had a reasonable expectation of success in finding the claims obvious.  The Board based its decision on the existence of anti-CGRP mAbs from other species, which would have provided sufficient motivation for the skilled worker to make humanized counterparts, and for the reasonable expectation of success that the claims recited no limitations regarding safety or efficacy for any intended purpose (in this way differing from the method claims the Board found not to be obvious over the same or related art as discussed above).  On this basis, the Board rejected Teva's argument that Lilly had a burden of establishing a reasonable expectation from the cited art for treating any disease or condition.

(In a side note, Teva had challenged the Board's decision based on the purported unconstitutionality of the APJs under the Court's decision in Arthrex, Inc. v. Smith & Nephew, Inc., 941 F.3d 1320 (Fed. Cir. 2019).  After the Supreme Court's decision in United States v. Arthrex, Inc., 141 S. Ct. 1970 (2021), during the pendency of this appeal, the panel gave Teva the choice of a hearing on the merits of the appeal or request for an immediate remand to the Board for resolution of the Arthrex question.  Teva chose this appeal on the merits, and the Federal Circuit's opinion followed.)

The Federal Circuit affirmed, in an opinion by Judge Lourie joined by Judges Bryson and O'Malley.  The panel rejected Teva's argument that the Board erred in finding a motivation and basis for the skilled worker to combine the cited art that differed from what Lilly had argued in this regard.  The difference, Teva maintained, was that under Lilly's purported argument there would need to be a therapeutic aim implicating safety and efficacy for the claimed anti-CGRP antibodies while in the Board's consideration it did not.  The Federal Circuit agreed with the Board that this was not a case where the Board "deviate[d] from the grounds in the petition and raise its own obviousness theory," citing Sirona Dental Sys. GmbH v. Institut Straumann AG, 892 F.3d 1349, 1356 (Fed. Cir. 2018).  In a nuanced argument, the panel found that the Board's appreciation of the motivation to make the claimed antibodies was to make humanized antibodies for treating human disease, based on "[c]ommon sense and scientific reality."  But the needed motivation was to make the antibodies not to use the antibodies to treat disease.  For the panel, "the relevant inquiry—which the Board extensively analyzed—is whether those [safety and efficacy] concerns would have dissuaded a skilled artisan from making the claimed antibodies to study their therapeutic potential in the first place."  That not being the case, the panel held that the Board had properly considered and was convinced by Lilly's evidence for a motivation to combine sufficient to support the Board's obviousness determination.  The panel noted that the Board had not disregarded Teva's arguments regarding safety and efficacy, according to the opinion; rather, it had considered the evidence in making a factual finding supported by substantial evidence to which the Court was obligated to defer.

Teva also argued more specifically that the Board had relied upon "unsupported interpretations of isolated statements in the prior art to find a motivation to study or use humanized anti-CGRP antibodies."  The panel noted that Lilly provided evidence, including expert testimony, to the contrary.  But the basis for the Court's rejection of Teva's arguments is that "[b]ut what a piece of prior art teaches presents a question of fact that is reviewed for substantial evidence," citing In re Warsaw Orthopedic, Inc., 832 F.3d 1327, 1332 (Fed. Cir. 2016), and In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000).  Under this deferential review, the panel held that the Board did not err in finding a reasoned basis for the skilled worker to combine the references.

The panel also considered and rejected Teva's arguments that the Board's determination that Teva's evidence for secondary considerations (or objective indicia) of non-obviousness failed due to a lack of nexus between the evidence and the claimed invention.  This evidence was related to both Teva's own (AJOVY®) and Lilly's (Emgality®) anti-CGRP mAb products with regard to "industry-wide acclaim, satisfied a long-felt need, achieved unexpected results, faced industry skepticism, and achieved commercial success" (i.e., almost all the secondary considerations), as well as licenses with third parties for its products falling within the scope of the claims.  With regard to the Board's lack-of-nexus determination, the panel acknowledged the presumption that a nexus exists if tied to a specific product "that is the invention disclosed and claimed," under Fox Factory, Inc. v. SRAM, LLC, 944 F.3d 1366 (Fed. Cir. 2019).  However, under certain circumstances there can be unclaimed features of such a commercial product along a continuum that can affect the nexus determination under this precedent.  Although the Court found that the "rule" the Board distilled from the Court's precedent was flawed and error, the panel held that the Board nevertheless conducted the proper nexus assessment in finding Teva was not entitled to the nexus presumption that can attach to a successful commercial product and that its error was thus harmless.  That assessment was consistent with the Court's rubrics set forth in Immunex Corp. v. Sandoz Inc., 964 F.3d 1049, 1067–68 (Fed. Cir. 2020), in the distinctions the panel appreciates between this invention and the one in Immunex.  In that case, the antibodies were disclosed and claimed based on structure whereas here they are claimed with regard to their function.  The Court cited its decision in Amgen Inc. v. Sanofi, 987 F.3d 1080, 1087 (Fed. Cir. 2021) (acknowledging in a footnote that the Amgen decision was rooted in Section 112 considerations), that antibodies claimed by function can be broad (or overbroad) because they do not define antibodies falling within the scope of the claims by structural limitations.  As a result, the panel opined that "[a] claim to 'anything that works' hardly has a nexus to any particular product."  Once again, the panel found that the Board's factual determinations were sufficient to support by substantial evidence its determination that there was a lack of nexus here between the parties' commercial products and the claimed invention.

The panel also rejected Teva's arguments that the third party licenses were sufficient to show the required nexus.  This decision rested on those licenses encompassing 188 patents (including the ones at issue here) and that the royalty obligations did not depend on whether these patents were invalidated or not.

The final decision, Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., was the only non-precedential decision and was directed to the Board's determination that the challenged claims of Teva's U.S. Patents 9,346,881, 9,890,211, and 8,597,649 were obvious.  In a summary opinion by Judge Lourie joined by Judges Bryson and O'Malley, the Court affirmed the Board's obviousness determination, substituting any detailed explication of the Board's decision and the panel's own rationale by stating:

In the two consolidated appeals, the parties made substantively identical arguments, mostly copied and pasted verbatim from one case to the other.  Teva included the following footnote in its opening brief:

In a second decision issued the same day, the Board also held unpatentable the challenged claims of three related composition patents.  That decision, which is materially identical in reasoning, is the subject of Teva's companion appeal no. 20-1747.  Teva's arguments in the two appeals are the same . . . [emphasis in opinion].

Lilly, not disagreeing with this sentiment, the panel asserted that "[d]uring the combined oral argument in the two consolidated appeals, neither party argued that any one of the six appeals should be decided differently from the others."  Accordingly, the Court based this opinion on its opinion affirming the Board's obviousness determination in Teva's other appeal of rejection of its monoclonal antibody claims for being obvious.

Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Bryson, and O'Malley
Opinion by Circuit Judge Lourie

Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Bryson, and O'Malley
Opinion by Circuit Judge Lourie

Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Bryson, and O'Malley
Opinion by Circuit Judge Lourie

Bio-Rad Laboratories, Inc. v. International Trade Comm. (Fed. Cir. 2021)

By Kevin E. Noonan --

Last week, the Federal Circuit affirmed imposition of an exclusion order under 19 U.S.C. § 1337 (Section 337 of the Tariff Act of 1930) by the Federal Trade Commission against 10X Genomyx (an intervenor in this appeal) over importation of patented microfluidic chips, in Bio-Rad Laboratories, Inc. v. International Trade Commission.  (10X Genomyx obtained a similar exclusion order against Bio-Rad in a case appealed last month; see "Bio-Rad Laboratories, Inc. v. Int'l. Trade Comm".)

In this action, Bio-Rad filed a complaint against 10X Genomyx alleging that importation of certain microfluidics chips infringed claims of U.S. Patent Nos. 9,500,664, 9,636,682, and 9,649,635.  Representative claims set forth in the opinion are these:

The '664 patent:

1.  A system for forming a plurality of sample-containing droplets suspended in a back- ground fluid, comprising:
    a substrate having a bottom surface and a top surface;
    a sample well, a background fluid well, and a droplet well each having an upper region protruding from the top surface of the substrate;
    a network of channels formed in the bottom sur- face of the substrate and fluidically interconnecting the sample well, the background fluid well, and the droplet well; and
    a droplet generation region defined by the network of channels and configured to generate sample-containing droplets suspended in the background fluid;
    wherein the droplet generation region is de- fined by the intersection of a first channel, a second channel, and a third channel;
    wherein the first channel is configured to transport sample-containing fluid from the sample well to the droplet generation region, the second channel is configured to transport background fluid from the background fluid well to the droplet generation region, and the third channel is configured to transport sample-containing droplets from the droplet generation region to the droplet well; and
    wherein the substrate and the upper region of each well are injection molded as a single piece.

The '682 patent:

14.  A system for generating droplets, comprising:
    a device including a row of sample wells each configured to receive sample-containing fluid, a row of continuous-phase wells each configured to receive continuous-phase fluid, and a row of droplet wells, the device also including a corresponding channel network for each sample well, the channel network including a droplet-generation region and fluidically connecting the sample well to one of the continuous-phase wells and one of the droplet wells;
    a holder for the device;
    a gasket configured to be attached directly to the holder, such that the gasket extends over each sample well, each continuous-phase well, and each droplet well; and
    an instrument configured to
        (a) receive an assembly including the device, the holder, and the gasket,
        (b) engage the gasket with a manifold, and
        (c) apply positive pressure and/or negative pressure to the device via the manifold, such that sample-containing fluid flows from each sample well to the corresponding droplet-generation region, continuous-phase fluid flows from each continuous-phase well to the corresponding droplet-generation region, and sample-containing droplets flow from each droplet-generation region to the corresponding droplet well.

The '635 patent:

1.  A system to form and concentrate an emulsion, comprising:
    a device including a sample well configured to receive sample-containing fluid, a continuous-phase well configured to receive continuous-phase fluid, and a droplet well, the device also including a channel network having a first channel, a second channel, and third channel that meet one another in a droplet-generation region; and
    an instrument configured to operatively receive the device and to create
        (a)    a first pressure differential to drive sample- containing fluid from the sample well to the droplet-generation region via the first channel, continuous-phase fluid from the continuous-phase well to the droplet-generation region via the second channel, and sample-containing droplets from the droplet-generation region to the droplet well via the third channel, such that the droplet well collects an emulsion including sample- containing droplets disposed in continuous-phase fluid, and
        (b)    a second pressure differential to decrease a volume fraction of continuous-phase fluid in the emulsion, after the emulsion has been collected in the droplet well, by selectively driving continuous-phase fluid, relative to sample-containing droplets, from the droplet, from the droplet well via the third.

(wherein the text in italics and boldface is the claim term at issue).

The technology at issue was related to microfluidics chips for performing bioanalytic assays using small amounts of sample contained in microdroplets, defined in the opinion as "a contiguous amount of one type of fluid that is encapsulated within a different fluid," wherein "the inner fluid is aqueous or water-based, while the outer fluid is oil" in typical embodiments.  Generally, the sample is contained in the aqueous inner fluid.  An advantage of this arrangement was that each sample could be subject to chemical reactions in its own droplet (a "mini-test tube" according to the '664 patent) and that a larger number of chemical reactions can be performed in parallel.  Such reactions are performed on microchips as claimed in the patents-at-issue (the opinion noting that such microchips were known in the art at the priority dates of these patents).

As set forth in the opinion, the named inventors of the asserted patents previously worked for a company (QuantaLife, Inc.) that was thereafter acquired by Bio-Rad.  These inventors had agreed in their employment contracts with QuantaLife to promptly assign to the company their rights to the provisional applications that matured into the three patents-in-suit, which they assigned to Bio-Rad after the acquisition.  These inventors later left Bio-Rad and formed 10X Genomics, where they developed the technology asserted by Bio-Rad to infringe the patents-in-suit.  Two embodiments of these chips were at issue in this case:

• GEM Chips, having "input wells for three different materials—gel beads, sample, and oil—and one output well to collect droplets.  The microfluidic channels on the GEM Chips intersect each other such that the gel bead and sample fluid are mixed at a first intersection, the resulting mixture enters into a microfluidic channel referred to as a 'singulation channel,' and the mixture then mixes with the oil at a second intersection."

• Chip GB, which 10X Genomyx utilizes "to generate droplets that are used to make the gel beads that are packaged with the GEM Chips and sold to customers.  The Chip GB contains one input well that holds an aqueous monomer solution, a second input well that holds oil, and channels from each of the wells that intersect each other to allow for the formation of droplets that are collected in a droplet well.  Over time, the monomers within each droplet polymerize, and the droplet becomes a gel bead."

Responsive to Bio-Rad's complaint, an Administrative Law Judge (ALJ) granted summary determination that the doctrine of assignor estoppel precluded 10X Genomyx from challenging the validity of the asserted patents.  The ALJ then construed the claims with regard to the term "droplet-generation region" to mean "the intersection of (1) a sample-containing dispersed phase fluid inlet channel, (2) a continuous phase fluid inlet channel, and (3) a droplet outlet channel."  The parties agreed that the term "sample" meant "a compound, composition, and/or mixture of interest, from any suitable source(s)."

Under this construction, the ALJ determined that 10X Genomyx's GEM Chips infringed the three patents, but that while the GB Chips infringed the claims of the '682 and '635 patents they did not infringe asserted claims 1 and 14 of the '664 patent because the monomer solution used with those chips was not a "sample" under the agreed-upon construction.  The Commission reviewed the ALJ's findings and adopted them, that the GEM chips infringed the three asserted patents (either literal, induced, or contributory infringement) but that the GB chips did not literally infringe the '644 patent.  The parties appealed each of the adverse determinations against them.

The Federal Circuit affirmed, in an opinion by Judge Lourie, joined by Judges Newman and Dyk.  With regard to Bio-Rad's appeal, the panel addressed two assertions that the ALJ erred.  The first was that because the GB chips did not involve a sample they did not have structures corresponding to "a 'sample well,' a sample channel, sample-containing droplets, or the claimed 'droplet generation region.'"  Second, Bio-Rad argued that due to the structural nature of the elements of the claims (wells and channels), infringement could not depend on what was in those wells and channels.  The "sample" limitation was assessed based on the parties' agreed-upon definition (which was taken from the '664 specification), and the Federal Circuit found no error in the ALJ relying on witness testimony that what was encapsulated in 10X Genomyx's GB Chip was not a sample under the agreed-upon definition but rather was "an input for a reagent production process" (emphasis in opinion).  This determination was also consistent with distinctions made in the '664 specification regarding the differences between a sample ("something that the customer cares about and wants to analyze") and a reagent ("which 'are of no interest'").  And this interpretation was also consistent with exemplified samples ("blood and plasma, and research samples such as culturued [sic] cells or bacteria") and reagents, defined as ""a compount [sic], set of compounds, and/or composition that is combined with a sample in order to perform a particular test(s) on the sample")(emphasis in opinion).  Bio-Rad's challenge was on these definitions, which they argued imported unsupported additional limitations into the claim term and were based on faulty conclusions (such as the monomer being "of no interest" under circumstances where "10X care-fully designed the monomer solution with particular concentrations of ingredients to serve as a gel bead precursor solution").  The Court agreed with the Commission and 10X Genomyx that Bio-Rad's arguments in this regard were directed to the Commission's factual determinations, and that under the Administrative Procedures Act the Commission's factual determinations were entitled to deference and "substantial evidence" review (which Bio-Rad did not satisfactorily challenge).  In this regard, the opinion states that "[t]he compelling factor here is the distinction between 'samples' and 'reagents'" as set forth (and relied upon by the Commission) in the '644 patent specification.  And, in particular, the panel did not find that consideration of the term "of interest" in construing the meaning of the claims and applying that construction to 10X Genomyx's GB chips imported any untoward subjectivity to the analysis.

Turning to Bio-Rad's second argument, the Federal Circuit considered this argument to "fail[]" for several substantive and procedural reasons.  The opinion states that it is "not clear" that Bio-Rad made this argument before the Commission, and accordingly should be precluded from presenting it on appeal in the first instance, citing Interactive Gift Express, Inc. v. CompuServe Inc., 256 F.3d 1323, 1346 (Fed. Cir. 2001).  Even if this procedural hurdle had been overcome, the panel asserted Bio-Rad would not prevail because its argument rested on "rewriting the claims in an oversimplified form and removing all limitations that differentiate the recited structures from each other."  The opinion illustrates this defect in Bio-Rad's argument by comparing the description of what is claimed in their brief with the actual claims, saying that the former "is not remotely close to what the claim says" it is.  "Inventors are masters of their claims, and the words they use to describe and claim their invention are decisive and binding," said the Court, and in the panel's view the '664 inventors did not claim their invention as broadly as it would need to have been claimed for Bio-Rad to prevail in its infringement argument here.  It was the inventors' decision "to characterize the wells and channels based on the material contained within them," according to the Court, and this choice cannot be "escaped" by recourse to the principle that "apparatus claims cover what a device is, not what a device does."  See Hewlett-Packard Co. v. Bausch & Lomb, Inc., 909 F.2d 1464, 1468 (Fed. Cir. 1990) (emphasis in original opinion).

10X Genomyx's appeal challenged the Commission's determination that its GEM chips infringed the asserted claims of the three patents-in-suit.  The first of two challenges by 10X Genomyx was based on whether their GEM chips contained the "droplet-generating region" required by the claims.  10X Genomyx's other challenge was directed to whether the evidence supported the Commission's determination regarding indirect infringement.  The challenge regarding whether GEM chips comprised the "droplet-generating region" was on claim construction, where 10X Genomyx asserted this alternative construction of the term:

[T]he intersection of the sample input channel that receives the dispersed phase fluid from the sample well, the oil input channel that receives the continuous-phase or background fluid from the oil well, and the droplet outlet channel that outputs to the droplet well, at which droplets are generated.

Bio-Rad (and the Commission) countered that 10X Genomyx had waived this argument three times:  "first, by failing to propose it in the parties' Joint Claim Construction Chart; second, by failing to seek review by the Commission of the ALJ's waiver finding; and third, by failing in its principal brief to ask this court to overturn the ALJ's waiver finding."  The Court was not convinced, citing instances in the record (including that the construction proposed here was identical to 10X Genomyx's initial construction asserted before the ALJ and maintained before the Commission), and that this consistent assertion of its construction did not constitute waiver that would preclude 10X Genomyx from making its alternative claim construction argument on appeal.

Nevertheless, on the merits, the panel found that the ALJ had correctly construed the term, based on the plain meaning of the claims and the specifications of the patents-in-suit.  The Court held that 10X Genomyx's proposed alternative construction would impermissibly impose requirements on the claimed invention not supported by the intrinsic evidence.  The Court also rejected 10X Genomyx's argument that the ALJ erred by applying the doctrine of assignor estoppel to preclude it from challenging construction based on the prior art, for the simple reason that the Court found evidence in the record that the ALJ had permitted these art-based challenges and that they had failed (which is not the same thing).  The opinion states that the ALJ had properly construed the claims using the intrinsic evidence under Phillips v. AWH Corp., 415 F.3d 1303, 1312–15 (Fed. Cir. 2005) (en banc), and the fact that prior art considerations did not make their way into the Commission's opinion (which the Court termed "less relevant arguments") did not indicate error.

With regard to the Commission's finding of indirect infringement, the Federal Circuit recognized 10X Genomyx's argument to be a factual one (was there enough evidence presented to support the determination?) that is entitled to the substantial evidence standard of review.  The facts at issue revolved around whether 10X Genomyx had knowledge of the patents (on contrast with the priority applications, where such knowledge was not in doubt).  In finding that the Commission's determination was supported by substantial evidence, the opinion states that "10X's various arguments attempt to distract from the reality of this case: named inventors of the asserted patents sold their company and patent rights to Bio-Rad, worked for Bio-Rad for a short time, left Bio-Rad to start a new company, and launched new products that have been determined to infringe the patents they assigned to Bio-Rad."  In addition, the opinion states that 10X Genomyx's arguments "largely attack the ALJ's credibility determinations and weighing of the evidence" (which fails the substantial evidence challenge), particularly with regard to the ALJ's credibility determinations of the witnesses (including the named inventors).  And regarding the existence of non-infringing uses relevant to the Commission's contributory infringement determination, the Court rejected 10X Genomyx's assertion of "hypothetical" systems (which 10X Genomyx asserted were relevant due to the statutory language that an accused product be "suitable" for non-infringing use) as being contrary to precedent (for which the panel sets forth examples including Fujitsu Ltd. v. Netgear Inc., 620 F.3d 1321, 1330–31 (Fed. Cir. 2010), and Golden Blount, Inc. v. Robert H. Peterson Co., 438 F.3d 1354, 1363 (Fed. Cir. 2006).  In sum, because "[i]t is not within [the Court's] purview to reweigh the evidence or to question the ALJ's credibility determinations" the Court affirmed the Commission's infringement determinations against 10X Genomyx.

Over the past six weeks, 10X Genomyx has obtained an exclusion order against Bio-Rad's importation of certain of their microfluidic chips over 10X Genomyx's patents and Bio-Rad in this case has obtained an exclusion order against 10X Genomyx's importation of certain of their microfluidic chips over Bio-Rad's patents.  The relationship and history between the companies argues against settlement, but under these circumstances settlement seems a sensible solution for both parties (depending of course on the relative market share and competitive positions of the parties excluded goods).

Bio-Rad Laboratories, Inc. v. International Trade Comm. (Fed. Cir. 2021)
Panel: Circuit Judges Newman, Lourie, and Dyk
Opinion by Circuit Judge Lourie

Bio-Rad Laboratories, Inc. v. Int'l. Trade Comm. (Fed. Cir. 2021)

By Kevin E. Noonan --

Last month, the Federal Circuit affirmed an exclusion order imposed by the International Trade Commission against Bio-Rad for importing infringing microfluidic systems and components used for gene sequencing or related analyses, in Bio-Rad Laboratories, Inc. v. Int'l. Trade Comm.

The ITC's decision followed a complaint by 10X Genomics, an intervenor in this appeal, for infringement of U.S. Patent Nos. 9,689,024, 9,695,468, and 9,856,530.  An ITC Administrative Law Judge found importation of the accused articles infringed claims in each of the asserted patents, that Bio-Rad had not established that the patents were invalid, and that 10X Genomics practiced the claims (and thus satisfied the "domestic industry" requirement of the Tariff Act of 1930, 19 U.S.C. § 1337(a)(2)).  Also, the ALJ rejected Bio-Rad's affirmative defense that it was a co-owner of these patents under terms of a prior employment contract with certain of the inventors.

The following claims are representative for each of the asserted patents:

Claim 1 of the '024 patent:

1.  A method for sample preparation, comprising:
    a) providing a droplet comprising a porous gel bead and a target nucleic acid analyte, wherein said porous gel bead comprises at least 1,000,000 oligonucleotide molecules comprising barcode sequences, wherein said oligonucleotide molecules are releasably attached to said porous gel bead, wherein said barcode sequences are the same sequence for said oligonucleotide molecules;
    b) applying a stimulus to said porous gel bead to release said oligonucleotide molecules from said porous gel bead into said droplet, wherein upon release from said porous gel bead, a given oligonucleotide molecule from said oligonucleotide molecules attaches to said target nucleic acid analyte; and
    c) subjecting said given oligonucleotide molecule attached to said target nucleic acid analyte to nucleic acid amplification to yield a barcoded target nucleic acid analyte.

Claim 1 of the '468 patent:

1.  A method for droplet generation, comprising:
    (a) providing at least 1,000,000 oligonucleotide molecules comprising barcode sequences, wherein said barcode sequences are the same sequence for said at least 1,000,000 oligonucleotide molecules, wherein said at least 1,000,000 oligonucleotide molecules are releasably attached to a bead, wherein said bead is porous;
    (b) combining said at least 1,000,000 oligonucleotide molecules and a sample comprising a nucleic acid analyte each in an aqueous phase at a first junction of two or more channels of a microfluidic device to form an aqueous mixture comprising said at least 1,000,000 oligonucleotide molecules attached to said bead and said sample; and
    (c) generating a droplet comprising said at least 1,000,000[ ]oligonucleotide molecules attached to said bead and said sample comprising said nucleic acid analyte by contacting said aqueous mixture with an immiscible continuous phase at a second junction of two or more channels of said microfluidic device.

Claim 1 of the '530 patent:

1.  A method for nucleic acid preparation or analysis, comprising:
    (a) providing:
        (i) at least 1,000 gel beads;
        (ii) releasably attached to each of said at least 1,000 gel beads, at least 1,000 barcode molecules comprising identical barcode sequences that are distinct from barcode sequences of at least 1,000 barcode molecules releasably attached to any other gel bead of said at least 1,000 gel beads; and
        (iii) a plurality of cells each comprising a plurality of polynucleotide molecules;
    (b) generating a plurality of droplets, wherein at least 1,000 droplets of said plurality of droplets each comprise:
        (i) a single gel bead from said at least 1,000 gel beads; and
        (ii) a single cell from said plurality of cells; and
    (c) in each of said at least 1,000 droplets, using said plurality of polynucleotide molecules from said single cell and barcode molecules of said at least 1,000 barcode molecules from said single gel bead to generate a plurality of barcoded polynucleotide molecules,
    wherein said barcode molecules become detached from said gel bead.

The factual history as set forth in the Federal Circuit's opinion is as follows.  Two of the named inventors of the asserted patents previously worked for a company (QuantaLife, Inc.) that was thereafter acquired by Bio-Rad.  These inventors had agreed in their employment contracts with QuantaLife to promptly disclose and assign to the company "the full details of any and all ideas, processes, recipes, trademarks and service marks, works, inventions, discoveries, marketing and business ideas, and improvements or enhancements to any of the foregoing ("IP")" that they "conceive[d], develop[ed] or create[d] alone or with the aid of others during the term of Employee's employment with the Company," and assign any such IP to the company (emphasis added).  These inventors signed similar agreements with Bio-Rad after the acquisition.

These inventors then left Bio-Rad in April 2012 and formed 10X Genomics in July 2012, where they developed the technology claimed in the asserted patents.  As set forth in the opinion, the 10X Genomics technology had a "gel bead in emulsion" (GEM) architecture that differed from the more conventional "capsule-in-capsule and capsule-in-droplets architecture."  The relevant features of this technology as claimed included that it "involves 'partitioning nucleic acids, DNA or RNA, in droplets together with gel beads that are used to deliver the barcodes into the droplet,' where the 'barcodes are released from the gel beads using a stimulus.'"  According to the opinion, there was no evidence that the inventors conceived of their technology prior to January 2013.

The basis for 10X Genomics' complaint was that Bio-Rad's products practiced the invention claimed in each asserted patent.  With regard to the '024 patent, the ALJ determined that Bio-Rad's accused methods practiced the step of "applying a stimulus to said porous gel bead to release said oligonucleotide molecules from said porous gel bead" (emphasis in opinion).  Bio-Rad unsuccessfully contended that the stimulus in its method acted on the oligonucleotides themselves rather than the gel bead, but the ALJ held (and the Commission affirmed) that the oligonucleotides were part of the gel bead and thus Bio-Rad's method satisfied this limitation.  For the '468 patent, Bio-Rad argued a distinction over the claim requirement of  "combining said at least 1,000,000 oligonucleotide molecules and a sample comprising a nucleic acid analyte . . . at a first junction of two or more channels of a microfluidic device to form an aqueous mixture."  Bio-Rad argued that the sample and oligonucleotide combination did not form an aqueous mixture at the first junction of the apparatus but were separate until droplets formed thereafter.  The ALJ disagreed based on testimony from 10X Genomics' expert, and the Commission agreed.  Concerning the '530 patent, Bio-Rad argued that its method did not fulfill the ALJ's construction of the claim that the second step (generating at least 1,000 droplets) was complete prior to the third step ("generating a plurality of barcoded polynucleotide molecules").  Bio-Rad supported this argument by the contention that the enzymes that provide the stimulus in its product "begin to form barcoded molecules immediately upon droplet formation" rather than after at least 1,000 droplets are formed.  The ALJ rejected this argument because the evidence showed that in practice the enzyme did not act sufficiently quickly to have "finish[ed] cleaving all barcoded molecules from the gel bead within the droplets before 1,000 droplets are formed."

The ALJ also rejected Bio-Rad's assertions that the 10X Genomics' product did not practice the invention claimed in the '530 patent any more than its own product did, a decision affirmed by the Commission on a slightly different basis, as well as rejecting Bio-Rad's argument that the claims of the '530 patent were indefinite.

Turning to Bio-Rad's affirmative defense that it was a co-owner of the asserted patents, the ALJ rejected the argument because there was no evidence that the invention(s) claimed in these patents had been conceived prior to January 2013 (after the inventors had left Bio-Rad's employ) and "'[n]o provision of any of the applicable contracts governs future inventions' merely because the future inventions 'are based on or developed from work done during employment.'"  In agreeing, the Commission also stated that the "ideas" identified by Bio-Rad purportedly worked on by the inventors during their employment terms were too "generic" to support co-ownership because the lacked the specifics required by the claims (and in particular that their work at Bio-Rad involved "droplet-in-droplet" not "gel-bead" architecture).  Also supporting the Commission's decision was their determination that many of the ideas asserted by Bio-Rad were to be found in Bio-Rad's prior art U.S. Patent No. 9,347,059 that named one of the inventors (showing, according to the Commission, that Bio-Rad had received the "benefit of its bargain" from the employment contract).

The Commission having affirmed the ALJ's decision, this appeal followed.

The Federal Circuit affirmed, in a decision by Judge Taranto joined by Judges Chen and Stoll.  The Federal Circuit held that substantial evidence supported the Commission's decision that Bio-Rad's accused imported articles infringed the asserted claims of the '024 patent.  The opinion notes that the plain meaning of the claim language recites that the oligonucleotides are releasably attached to the porous gel bead, and release is caused by applying a stimulus; Bio-Rad's system satisfies those requirements according to the Court.  The panel rejected Bio-Rad's arguments to the contrary, based on the distinction between the oligonucleotides and the porous gel bead being distinct entities, and differences in how its stimulus differs from what is exemplarily disclosed in the '024 specification.

The Court also rejected Bio-Rad's distinctions between what is claimed in the '468 patent and its accused imported articles based on the details of mixing the nucleic-acid-sample solution and reagent solution.  The opinion states that the evidence Bio-Rad relied upon to make a spatial distinction between where these solutions are mixed and where droplets are formed was "hazy" and that without record evidence supporting Bio-Rad's argument the Court "cannot say that the Commission lacked substantial evidence to find that Bio-Rad infringed the '468 patent."

The opinion also set forth and rejected the arguments Bio-Rad raised against the Commission's determination that its accused imported articles infringed the asserted claims of the '530 patent.  As a threshold matter the opinion states that:

Bio-Rad's argument must fail unless the Commission erred, as a matter of claim construction, in determining that the claim permits some barcode detachment (from the gel of the bead) to occur before 1,000 droplets are formed—as long as the claim-required number of detachments occur after 1,000 droplets have formed.

But Bio-Rad made no objection or argument regarding the Commission's claim construction, and the panel found none.  The claim recites that the second step of claim 1 of the '530 patent be completed before the third step.  But the panel opinion states that "[c]ritically, that conclusion does not mean, and the claim language does not require, that there be no barcode detachment before 1,000 droplets are generated" (which was the basis for Bio-Rad's argument).  The opinion states that the Commission's determination was supported by substantial evidence that "barcode molecules are not released from the gel beads instantaneously and that, instead, the barcoding process merely begins to occur upon droplet formation, with enough barcode detachment still occurring after 1,000 droplets are formed to meet the claim requirement" and, if that was the case, the Commission was correct in finding that "[t]he fact that barcoding of other polynucleotides also happened before 1,000 droplets were generated is irrelevant."

Bio-Rad turned this argument on its head in contending that 10X Genomics' product did not practice the invention claimed in the asserted claims of the '530 patent and thus did not satisfy the domestic industry requirement in the statute for relief from the ITC under Section 1337(a)(2).  But because "[t]he test for satisfying the 'technical prong' of the [domestic] industry requirement is essentially [the] same as that for infringement, i.e., a comparison of domestic products to the asserted claims," Alloc, Inc. v. Int'l Trade Comm'n, 342 F.3d 1361, 1375 (Fed. Cir. 2003), the Federal Circuit also rejected this challenge to the Commission's determination.  According to the opinion, Bio-Rad failed to show the Commission's determination was not supported by substantial evidence, being based on documentary evidence and expert testimony.

Bio-Rad also asserted (and the Federal Circuit rejected) that the claims of the '530 patent are indefinite, which the panel reviewed de novo in the absence of any challenge to the Commission's material findings.  The opinion affirmed the Commission's determination that Bio-Rad had forfeited this defense by raising it for the first time during the Commission's consideration of the ALJ's determination (Bio-Rad did not contest this decision until its Reply brief below).  But in addition, the panel rejected the basis for Bio-Rad's indefiniteness contention, that the Commission had to clarify the ALJ's initial claim construction.  The opinion notes that "[m]odifications are proper and sometimes necessary steps as disputes sharpen during litigation," citing Pfizer, Inc. v. Teva Pharms. USA, Inc., 429 F.3d 1364, 1377 (Fed. Cir. 2005), and that in this case all that occurred before the Commission was "[m]ere amplification of an initial construction to resolve a material dispute about claim meaning," which "provides an even weaker potential basis for a suggestion of indefiniteness."

Finally, the Court turned to Bio-Rad's argument that it is a co-owner of the asserted patents based on an employment contract with some of the inventors.  As the Court understood Bio-Rad's contentions:

First, Bio-Rad asserts, if [inventors] Drs. Hindson and Saxonov, when working at Bio-Rad (or its predecessor QuantaLife), had ideas that contributed to the post-employment inventions at issue, and if those contributions would make them co-inventors (regardless of post-employment contributions to the inventions), then the assignment provisions required assignment of their co-ownership interest to Bio-Rad.  Second, Bio-Rad asserts, Drs. Hindson and Saxonov did in fact have such co-inventorship-qualifying ideas while employed at Bio-Rad (specifically, while working for QuantaLife).

The Court assessed these assertions under California law as matters of contract interpretation; under that law interpretation of a contract is a matter of law subject to de novo review according to the opinion.  The opinion comes directly to the point:  "Bio-Rad has furnished no persuasive basis for disturbing the Commission's conclusion that the assignment provisions do not apply to a signatory's ideas developed during the employment (with Bio-Rad or QuantaLife) solely because the ideas ended up contributing to a post-employment patentable invention in a way that supports co-inventorship of that eventual invention."  Specifically, the panel appreciated that the employment contracts by their terms were limited to intellectual property that arose in the course of employment at the time the inventors were employed by Bio-Rad's predecessor-in-interest, QuantaLife (i.e., "before the termination of employment").  Under these circumstances, the Court noted that "Bio-Rad does not argue, much less demonstrate, that a person's work, just because it might one day turn out to contribute significantly to a later patentable invention and make the person a co-inventor, is itself protectible intellectual property before the patentable invention is made."  For a patent, "the pertinent intellectual property does not exist until at least conception of that invention" the opinion states, citing, inter alia, Burroughs Wellcome Co. v. Barr Labs., Inc., 40 F.3d 1223, 1227–28 (Fed. Cir. 1994).  None of the precedent Bio-Rad advanced in support of its co-ownership argument was to the contrary (and remarkably did not support its argument in the Court's opinion), in particular Bd. of Trustees of the Leland Stanford Junior Univ. v. Roche Molecular Sys., Inc., 583 F.3d 832, 837 (Fed. Cir. 2009).  Finally, the panel understood California law to "recognize[] significant policy constraints on employer agreements that restrain former employees in the practice of their profession, including agreements that require assignment of rights in post-employment inventions" insofar as "[s]uch an agreement might deter a former employee from pursuing future work related to the subject matter and might deter a future employer from hiring that individual to work in the area."  And the panel did not find any reversible error by the Commission in deciding, on the merits, that nothing the inventors had done during the course of their employment had sufficient specificity to support Bio-Rad's claims of an ownership interest in any of the asserted patents.

Bio-Rad Laboratories, Inc. v. Int'l. Trade Comm. (Fed. Cir. 2021)
Panel: Circuit Judges Taranto, Chen, and Stoll
Opinion by Circuit Judge Taranto

Bayer Healthcare LLC v. Baxalta Inc. (Fed. Cir. 2021)

By Kevin E. Noonan --

Last week, the Federal Circuit affirmed a jury verdict against Baxalta Inc., Baxalta US Inc., and Nektar Therapeutics for infringing Bayer Healthcare's patent to human blood clotting factor conjugates in Bayer Healthcare LLC v. Baxalta Inc.

Bayer Healthcare sued Defendants on U.S. Patent No. 9,364,520, alleging willful infringement by Baxalta's product, Adynovate®.  This product is a recombinant human Factor VIII (the blood clotting factor responsible for causing Hemophilia A) having the protein structural domains A1-A2-B-A3-C1-C2, wherein the B portion was specifically modified by addition of polyethylene glycol (PEG).  PEGylation is important because Factor VIII has an 11-hour half-life which requires frequent injections and leads to reduced patient compliance.  The prior art had disclosed "random" modification of Factor VIII with PEG, which had "several drawbacks" due to the multiplicity of PEGylations sites ("158 lysines, the two N-termini, and multiple histidines, serines, threonines, and tyrosines") in the Factor VIII protein, which led to heterogeneity in the species produced, including ones having deleterious effects on Factor VIII activity and ones having a multiplicity of PEG residues conjugated to the protein.

The '520 patent specification disclosed site-specific PEGylation at a site not at an N-terminal amine; claim 1 is representative:

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.

(wherein the italicized portions of the claim identify claim language disputed in the litigation).

At trial, the District Court construed the term "isolated polypeptide conjugate" to mean "a polypeptide conjugate where conjugation was not random."  Specifically, the District Court held that during prosecution of the '520 patent, Bayer had disclaimed embodiments having random PEGylation.  Further, the District Court construed the term "at the B-domain" to mean "attachment at the B-domain such that the resulting conjugate retains functional factor VIII activity," rejecting Baxalta's proposed construction that the phrase should be construed to mean "at a site that is not any amine or carboxy site in factor VIII and is in the B-domain."  The District Court granted Defendants' pre-trial motion as a matter of law that there was no willful infringement, and a jury found that Defendants infringed claims 1-3 and 8 of the '520 patent.  The jury found against Defendants' counterclaim of non-enablement, and awarded Bayer $155,190,264 in reasonable royalty damages, based on a 17.78% royalty rate for $872,836,128 in Defendants' profits.  The District Court also denied Defendants' JMOL motions on the issues of infringement, enablement, and damages.  Bayer filed a motion under Federal Rule of Civil Procedure 59(a) for pre-verdict supplemental damages, which the District Court granted and awarded Bayer another $18,324,562.  The District Court also denied Bayer's motion for JMOL on willful infringement.  Both parties appealed.

The Federal Circuit affirmed, in an opinion by Judge Stoll, joined by Judges Newman and Linn.  The opinion first opined on the District Court's claim construction, which (because the District Court had not relied upon extrinsic evidence) was performed de novo, with regard to the interpretation of the terms "at the B-domain" and "random" PEGylation of the B portion of Factor VIII.  The opinion rejected Defendants' argument that the term "at the B-domain" should have been interpreted to exclude amine/lysine PEG conjugation.  The opinion sets forth its claim construction analysis by way of the factors enunciated in Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc):  plain meaning of the claim terms, the specification, and the prosecution history.  The Federal Circuit found the plain meaning of the term "'[a]n isolated polypeptide conjugate' in which PEG 'is covalently attached to the functional factor VIII polypeptide at the B-domain'" does not require any particular amino acid residue to be PEGylated, saying that the claim "broadly requires PEGylation at the B-domain as a region."  The panel identified statements in the specification that supported this construction, and while acknowledging that PEGylation at cysteine residues was expressly disclosed, held that this disclosure did not limit the scope of site-specific PEGylation to just cysteine residues.  The Federal Circuit also disagreed with Defendants that the specification disparaged amine/lysine PEG conjugation, expressly based on Indivior Inc. v. Dr. Reddy's Laboratories, S.A., 930 F.3d 1325 (Fed. Cir. 2019); Gaus v. Conair Corp., 363 F.3d 1284 (Fed. Cir. 2004); and SciMed Life Systems, Inc. v. Advanced Cardiovascular Systems, Inc., 242 F.3d 1337 (Fed. Cir. 2001) (although the opinion states that it was a close question).  Rather than disparaging or disclaiming any particular type of conjugation with PEG, the panel held that the '520 patent specification disparaged random PEGylation (which is not the same thing).  Finally, the opinion held that nothing in the prosecution history was to the contrary, specifically in that it did not contain "a clear and unmistakable surrender of claims directed to non-random amine/lysine PEGylation."  While art cited by the USPTO included amine/lysine conjugation sites, taken as a whole and as understood by a person of ordinary skill in the art, the Federal Circuit held the rejection and cited art was directed to random PEGylation.  (And Defendants' citation of statements made in the prosecution of related European Patent Application No. 11153287.4 were unavailing, both on the merits and, in agreement with the District Court, "varying legal and procedural requirements for obtaining patent protection in foreign countries might render consideration of certain types of representations inappropriate for consideration in a claim construction analysis of a United States counterpart.")

With regard to the term "random," the Federal Circuit rejected Defendants' argument that the District Court had erred by not expressly defining the term, thus improperly leaving construction of this term to the jury.  The panel held that the District Court had "resolved the parties' differences" with regard to this term by addressing (and rejecting) Defendants' arguments that "(1) that 'random' conjugation means any conjugation at amines or carboxy sites; and (2) that 'random' conjugation means all heterogenous conjugation."  The Federal Circuit understood the District Court's construction did not exclude any degree of heterogeneity from PEG conjugation but rather that Bayer had disparaged embodiments with "a high degree of heterogeneity" (which was the problem with prior art embodiments of PEGylated Factor VIII preparations that distinguished Bayer's invention).  Reciting the District Court's construction, the opinion states that the District Court found (correctly) that "non-random conjugation neither required that each FVIII protein in a product such as Adynovate® be PEGylated in the same places (homogeneity among conjugates in the product) nor required that every PEG on each FVIII protein be in the B-domain (homogeneity within each conjugate)."  Accordingly, the Federal Circuit held that limiting the term "random" with reference to construction of the term "isolated polypeptide conjugate" to mean "a polypeptide conjugate where conjugation was not random" sufficiently defined the meaning of the word "random" in the claimed context, and that this was consistent with other district court decisions, including denial of Defendants' motion in limine on this issue.

The panel also affirmed as being supported by substantial evidence the jury's infringement decision, and consequently, that the District Court did not err in denying Defendants' motion for JMOL.  The opinion provided a synopsis of the parties' evidence, including differing expert witnesses on infringement, supported by Baxalta's submissions to FDA regarding the specificity with which its Factor VIII product comprised "controlled, targeted chemical addition of 20 [kilodalton] PEG conjugates to this FVIII B-domain" (emphasis in opinion), statements inconsistent with random PEGylation.

Similarly, the Federal Circuit held that there was substantial evidence for the jury's rejection of Defendants' non-enablement defense, particularly with regard to embodiments comprising non-random lysine PEGylation.  According to the opinion, "Bayer presented substantial evidence from which a reasonable juror could find that the specification's disclosure of instructions as to the reaction conditions required to practice the claimed invention using cysteine PEGylation were sufficient to enable not only non-random cysteine PEGylation at the B-domain, but also non-random lysine PEGylation at the B-domain."  Somewhat in contrast to recent, more stringent applications of the Federal Circuit's standards for enablement (see Amgen Inc. v. Sanofi and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc.), this panel held that "the specification need not include a working example of every possible embodiment to enable the full scope of the claims," citing Alcon Rsch. Ltd. v. Barr Labs., Inc., 745 F.3d 1180, 1189–90 (Fed. Cir. 2014), and Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1336–37 (Fed. Cir. 2003).

Defendants also appealed the jury's damages calculations and the basis thereof.  While agreeing with the District Court in rejecting Bayer's expert's 50-50 split royalty rate, the panel disagreed with several other assertions of error by Defendants.  These included the basis for the 17.78% reasonable royalty rate, which Defendants' argued relied on a "a flawed and speculative methodology—namely, asking the jury to pick a rate between the range of feasible rates presented by [Bayer's expert] as the reasonable rate."  The Federal Circuit held that "[t]he district court properly exercised its discretion in allowing Bayer to ask the jury to select a rate between the range presented," within the confines of a damages expert using "reliable methodology for determining the range of possible hypothetical negotiation royalty rates."  When, as here, a jury's damages award "fell within the range suggested by the patentee's damages expert" the Federal Circuit stated it was supported by substantial evidence, citing Rembrandt Wireless Techs., LP v. Samsung Elecs. Co., 853 F.3d 1370, 1382 (Fed. Cir. 2017), and that the District Court had not erred in permitting the jury to received Bayer's damage expert's testimony.  Defendants had had (and had exercised) the opportunity to cross-examine Bayer's expert on his methodology and damaged calculation, according to the opinion, and "ultimately, the jury evaluated his opinions and adopted a rate within his proposed range."  In the Federal Circuit's opinion there was nothing improper about the jury's damages calculation or award.

Finally, Defendants argued that the District Court had violated their Seventh Amendment rights by awarding pre-judgment damages under Fed R Civ Pro 59.  In doing so, according to the Federal Circuit, the District Court used actual sales data instead of projected amounts and applied the same 17.78% royalty rate on the amount of these actual sales.  "Under these circumstances," said the Federal Circuit, "we are not persuaded that the District Court's award constitutes an impermissible additur or an otherwise 'bald addition of something which in no sense can be said to be included in the verdict,'" citing Dimick v. Schiedt, 293 U.S. 474, 486 (1935) (the remainder of the Court's opinion making it clear that its judgment was limited to the facts in this case).

Regarding Bayer's appeal on the District Court's grant of Defendants' motion for JMOL on willful infringement, the panel held that there was insufficient evidence of the necessary "state of mind" having "a specific intent to infringe at the time of the challenged conduct" to support willfulness, citing Halo Elecs., Inc. v. Pulse Elecs., Inc., 136 S. Ct. 1923, 1933 (2016) ("willful, wanton, malicious, bad-faith, deliberate, consciously wrongful, flagrant, or—indeed—characteristic of a pirate").  The panel affirmed the District Court's decision even though "there was no dispute that Baxalta was 'aware of the '520 patent,'" because "Bayer merely 'assume[d] that [Baxalta] knew Adynovate[®] infringed because it involved pegylation at the B-domain of factor VIII."  The Federal Circuit rendered this opinion even in the face of testimony by Defendants' witnesses "concerning their awareness of the patent application that issued as the '520 patent" and representations to FDA regarding non-random PEGylation in Defendants' Adynovate® product.

Bayer Healthcare LLC v. Baxalta Inc. (Fed. Cir. 2021)
Panel: Circuit Judges Newman, Linn, and Stoll
Opinion by Circuit Judge Stoll