Teva Pharms. Int’l GmbH v. Eli Lilly and Co., Appeal Nos. 2020-1747, -1748, -1750 (Fed. Cir. Aug. 16, 2021)

Eli Lilly and Co. v. Teva Pharms. Int’l GmbH, Appeal Nos. 2020-1876, -1877, -1878 (Fed. Cir. Aug. 16, 2021)

In this week’s Cases of the Week, the Federal Circuit reviewed .final written decisions from multiple inter partes reviews brought by Eli Lilly against Teva Pharmaceuticals patents relating to compositions and methods for treating headaches and other vasomotor symptoms. In Teva Pharms. v. Eli Lilly, the Patent Trial and Appeal Board had found that composition claims covering humanized antagonist antibodies targeting calcitonin gene-related peptide (“CGRP”) amino acids, such as the active ingredient in Teva’s AJOVY® and Lilly’s Emgality® migraine drugs, were obvious over the prior art. However, in Eli Lilly v. Teva Pharms., the Board had found that single-step method claims reciting administering an “effective amount” of the same compositions to treat vasomotor symptoms were not shown to be unpatentable over the same prior art. The Federal Circuit affirmed the Board’s decisions in both cases, in the process providing a helpful review of claim construction and obviousness issues relevant to composition and method claims, which may inform pharmaceutical patent practitioners’ approaches to both obviousness litigation and claiming strategies in prosecution.

As background, the challenged patents themselves explained that CGRP had previously been noted for its possible connection to vasomotor symptoms such as migraines and other vascular headaches. At the time of the inventions disclosed in the patents, the pathophysiology of migraines was not well-understood, although dilation of blood vessels was associated with and thought to exacerbate the pain symptoms of migraine. Thus, the role of CGRP as a vasodilator had informed the development of possible migraine treatments that sought to restrict the activity of CGRP in the body. The prior art included a clinical trial proving the efficacy of BIBN4096BS (“BIBN”), a nonpeptide CGRP-receptor antagonist, in the treatment of migraine, as well as in vivo studies in rats using anti-CGRP antibodies to inhibit CGRP-induced skin blood flow. The latter studies had found that while the small Fab’ fragment of the anti-CGRP antibodies (the portion that binds to the target antigen) was effective in blocking the effects of endogenous CGRP, the full-length antibody was not effective at the doses and incubation periods described in the studies. At the time, there was uncertainty concerning whether migraine medications needed to cross the blood-brain barrier to be effective, which impacted the Board’s analysis of the obviousness of the claimed large-molecule anti-CGRP antibodies in view of prior art disclosing the effective use of smaller CGRP-related molecules, such as BIBN and the antibodies’ Fab’ fragment, in inhibiting CGRP-induced vasodilation. 

Against this backdrop, the Court found in Teva Pharms. v. Eli Lilly that it would have been obvious to make and use the claimed anti-CGRP antibodies. Teva did not challenge the Board’s finding that each limitation of the challenged claims was disclosed in the prior art, but instead argued that the Board erred in finding a motivation to combine and in its failure to consider secondary considerations of nonobviousness.

Teva first contended that the Board erred by relying on a different motivation to combine from the one that Lilly asserted in its IPR petitions. While Lilly had asserted that a skilled artisan would have been motivated to make a humanized anti-CGRP antibody for therapeutic use in humans, the Board had found that a skilled artisan would have been motivated to make the antibody “merely to study or use it.” The Federal Circuit was not persuaded, finding that “[c]ommon sense and scientific reality dictate that scientists do not ‘study or use’ humanized antibodies with an end goal of treating diseases in test tubes or in rats,” and that the prior art therefore supported a motivation to humanize antibodies with the goal of treating human diseases, regardless of the Board’s phrasing. However, the Court simultaneously rejected Teva’s arguments that safety and efficacy concerns would have dissuaded a skilled artisan from making the claimed combination, finding that because the claims themselves were directed to compositions, the motivation to combine analysis ended at whether a skilled artisan would have been motivated to make the claimed antibodies—e.g., for further study with the goal of eventually treating humans—and did not extend to whether they would have been motivated to actually use the resulting antibodies to treat human disease.

Teva alternatively argued that Lilly cherry-picked portions of the prior art to support its asserted motivation to combine, and that the prior art as a whole did not support a motivation to further explore a full-length anti-CGRP antibody for use in humans. The Federal Circuit found that it was unsurprising that Teva disagreed with the Board’s interpretation of the prior art, but that substantial evidence nonetheless supported the Board’s determination, re-affirming the principle that “if two inconsistent conclusions may reasonably be drawn from the evidence in the record, the PTAB’s decision to favor one conclusion over the other is the epitome of a decision that must be sustained upon review for substantial evidence.”

The Court also considered Teva’s evidence of secondary considerations of non-obviousness, which focused on the success of AJOVY® and Emgality® and on Teva’s licensing of the challenged patents. The Board found that Teva had not demonstrated a nexus between these considerations and the challenged claims, and the Federal Circuit agreed, finding that Teva was not entitled to a presumption of nexus because the challenged claims were not “coextensive” with the asserted commercial products. In this analysis, the Court offered a comprehensive overview of its precedent concerning the coextensiveness requirement, noting that the degree of correspondence between a product and a patent claim falls along a spectrum, and that while a patentee was not required to prove perfect correspondence (e.g., that the product contains no material unclaimed features) to enjoy a presumption of nexus, it is required to demonstrate that “the product is essentially the claimed invention.” In this case, the Court relied on the broad, functional nature of the challenged claims’ limitations, which were directed to the claimed compositions’ ability to bind to the CGRP ligand, to the exclusion of specific structural limitations. Noting that “[a] claim to ‘anything that works’ hardly has a nexus to any particular product,” the Court found that the unclaimed structural features of the parties’ migraine drugs affecting their ability to perform that function—such as specific amino acid sequences critically affecting their binding affinity—were of particular importance to the coextensiveness analysis, and that Teva was not entitled to a presumption of nexus between its broad functional claims and the specific commercially successful compounds.

The Court also found no nexus between the challenged claims and Teva’s asserted licensing evidence, which was a broad portfolio license of 188 Teva patents with no meaningful analysis of the licensee’s economic motivation, and where Teva had conceded that the license and royalty payments would continue unabated regardless of the validity of the three challenged patents. As Teva had relied only on the presumption of nexus and the mere existence of the license in arguing nonobviousness, the Court affirmed the Board’s finding of no nexus and that it had properly disregarded the alleged secondary considerations of nonobviousness.

Because the Board properly found a motivation to combine and no relevant secondary considerations of nonobviousness, the Court affirmed the Board’s determination that the challenged composition claims were unpatentable over the prior art.

However, in Eli Lilly v. Teva Pharms., the Court also affirmed the Board’s finding that claims reciting a single-step method of administering an “effective amount” of those same compounds to treat headaches and other vasomotor symptoms were not shown to be unpatentable over the prior art. In that case, Lilly argued that the Board erred by construing the claim preambles (which recited, e.g., “a method for treating headaches in an individual”) and the term “effective amount” to require an expectation of unclaimed results; and that even under the Board’s constructions, the Board had applied too high a standard in determining whether a skilled artisan would have had a reasonable expectation of success in combining the teachings of the asserted prior art.

As to the claim preambles, Lilly argued that the Board erred in construing them as limiting to the extent that they required the claimed methods to be performed with an intentional purpose, contending that as a matter of law, a preamble containing only a statement of purpose cannot be a claim limitation. The Federal Circuit disagreed, noting that its precedent did not support Lilly’s proposed binary distinction between statements of mere intended purpose and limiting preambles, reaffirming that there is no “litmus test” or bright-line rule for determining whether a preamble is limiting. Reviewing its precedent on construing preambles, the Court noted that method claim preambles including statements of purpose are more often found to be limiting than such preambles to composition or apparatus claims. In this case, the Court found that the patents’ specification heavily supported a characterization of the invention as a method for treating vasomotor symptoms; that the preambles provided an antecedent basis for subsequent claim limitations (e.g., “administering to the individual”); and that the preambles gave meaning to the substantive claim requirement of administering an “effective amount,” which could not be determined without reference to the preambles. In this last regard, the Court distinguished cases involving patent claims covering administration of specified amounts of a compound, which would be the same regardless of the intended purpose.

Lilly also argued that the term “effective amount” could not support treating the preambles as limiting because dependent claiming required the term to encompass clinically ineffective doses. However, the Court found that the Board had properly construed “effective amount” based on the patents’ definition to be “an amount sufficient to effect beneficial or desired results,” which encompassed but did not require clinically effective results. As such, the Court concluded that Lilly’s arguments as to clinical effectiveness were irrelevant to its determination that the preambles were limiting.

Turning to Lilly’s “reasonable expectation of success” arguments, the Federal Circuit emphasized the distinction between a “motivation to combine” and a “reasonable expectation of success” in achieving the claimed invention, that a motivation to combine does not necessarily imply an expectation of success, and that a patent challenger in an IPR has the burden to prove both by a preponderance of the evidence. Because the preambles were found to be limiting, Lilly was required not only to prove that a skilled artisan would be motivated to combine the asserted prior art, but also that they would have expected success in administering a humanized anti-CGRP antibody for treating headaches and other vasomotor symptoms.

On the facts of this case, the Court first rejected Lilly’s arguments that the Board improperly required the prior art to disclose clinical efficacy data on anti-CGRP antibodies in order to find an expectation of success. The Federal Circuit agreed that a reasonable expectation of success need not rely on clinical data or any demonstration of certainty of success, which indeed might lead to a finding of anticipation rather than obviousness. However, while the Board had observed that the prior art did not disclose such data, and while such disclosures would have been important to its obviousness analysis, the Court found that the Board also considered whether the prior art contained any other “information,” “direction,” or “specific suggestion” that would have led to a reasonable expectation of success in the use of full-length anti-CGRP antibodies to treat vasomotor symptoms in humans. As such, the Court found that Lilly’s arguments misread the Board’s decisions, and declined to infer a demand for data from mere observations that the prior art did not include such data.

The Federal Circuit also considered Lilly’s arguments that the prior art otherwise suggested an expectation of success, and that the Board had improperly disregarded a reference that Lilly argued had “settled” the question of whether migraine treatments must pass the blood-brain barrier by the time of the patents’ inventions, such that a skilled artisan would have expected success from the use of larger full-length anti-CGRP antibodies as opposed to smaller molecules. On these points, the Court noted the uncertainty reflected in the prior art as a whole and the then-continuing debate on the blood-brain barrier question, and as in Teva Pharms. v. Eli Lilly, above, concluded that just because Lilly disagreed with the Board’s factual findings interpreting the prior art did not mean those findings were not supported by substantial evidence under the Court’s deferential standard of review.

Because the Board had properly construed the claims and Lilly had not shown a reasonable expectation of success in combining the teachings of the prior art, the Federal Circuit affirmed the Board’s decision finding that the challenged method claims were not shown to be unpatentable as obvious.

Teva Pharms. v. Eli Lilly is available here, and Eli Lilly v. Teva Pharms. is available here.

By Jason Wrubleski

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As we wrote in June, Gilbert Hyatt sued the Patent and Trademark Office in district court pursuant to 35 U.S.C. § 145. The district court ruled in his favor, directing the Director of the PTO to issue Hyatt patents for some of his claims. The district court thereafter awarded him costs as the prevailing party. In June this year, a panel of the Federal Circuit reversed the district court’s underlying decision. Thus, Hyatt can no longer be considered the prevailing party. Accordingly, this week, the Court vacated and reversed the district court’s award of costs to Hyatt.

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