Originally posted on IPKat.
In contrast to Teva, the claims in Wyeth were found not to be enabled, despite the full structure of the compound being included in the claim. In this case, the Patentee ran afoul of a definition in the description that the court imported into the claims and thereby increased the enablement requirements.
Legal background: The more you claim, the more you must enable
US patent law imposes two distinct sufficiency requirements under 35 U.S.C. section 112(a), written description and enablement (Evolve Insights). Only enablement was at issue in this case. The enablement test asks whether the specification teaches a skilled person how to make and use the claimed invention without undue experimentation. Amgen v Sanofi confirmed that this test is applied to the whole of what is claimed, not a favoured embodiment. As the Federal Circuit famously repeated, “[t]he more one claims, the more one must enable”.
Case background: Pursuing oncology billions
The patents in suit, US 10,603,314 and US 10,596,162, both related to the treatment of non-small cell lung cancer (NSCLC) that has stopped responding to the EGFR inhibitors gefitinib and erlotinib. The claimed solution was an irreversible inhibitor binding covalently to a specified cysteine in the ligand-binding pocket. Claim 1 of the ‘314 patent as granted required “administering daily to the patient” a composition comprising “a unit dosage” of such an inhibitor.
The examples supporting the invention were relatively thin. The specification noted that the inhibitor “may be any compound which binds to cysteine 773 of EGFR”, of which three examples were named (EKB-569, HKI-357 and HKI-272) and tested in vitro. Importantly, the specification defined “unit dosage” as a predetermined quantity “calculated to produce the desired therapeutic effect”, and noted that precise amount depended on the subject and on “the judgment of the practitioner”. The specification also offered a “general” daily dosage of about 0.5 to about 1000 mg/kg alongside a total daily dosage “projected” to be about 1 to 1000 mg.
Wyeth sued AstraZeneca for infringement by its oncology blockbuster Tagrisso (osimertinib) (2025 global revenue of USD 7.3 billion). AstraZeneca lost before the jury, which awarded Wyeth USD 107.5 million in damages, but won on a renewed motion for judgment as a matter of law, the district court holding that no reasonable jury could have found the claims enabled.
The definition of a unit dose
On appeal to the Federal Circuit, Wyeth’s first argument was that the district court had imported clinical safety and efficacy requirements into claims that contained none, so that all the claims demanded was a quantity capable of inhibiting EGFR and killing cancer cells. The Federal Circuit agreed with this premise but rejected the conclusion. Particularly, the Federal Circuit found that the claims imported no FDA-type standards, but Wyeth’s reading still ignored the key limitations of “administering daily” and “patient”. Read as a whole, reasoned the court, the claims “plainly require the daily administration of a unit dosage to a patient to achieve a therapeutic effect … not merely the identification of compounds capable of inhibiting EGFR activity in vitro” (p. 10).
Key to the court’s reasoning was the fact that the Patentee had defined “unit dosage” in the specification by reference to a quantity “calculated to produce the desired therapeutic effect”. The district court adopted that definition before trial without challenge. Unfortunately for the Patentee, having written a functional dosing limitation into its own claims by way of its own glossary, the Federal Circuit found that it was then obliged to enable it.
Projected, general and untested
Turning to the enablement question, the Federal Circuit found that the specification “leaves the determination of the claimed ‘unit dosage’ entirely to the knowledge of the skilled artisan” (p. 14). There were no worked examples of unit dosages calculated to be safe and efficacious, and no teachings on how to extrapolate from the in vitro results to a therapeutic dose in patients.
The numerical ranges also could not save the claims in the Federal Circuit’s view. It was noted that the specification itself called them “general” and “projected”, with no account of how they were derived, how a skilled person would choose within them, or how they related to the therapeutic effect the definition demanded.
Additionally, AstraZeneca established, unrebutted, that for at least two of the three disclosed compounds every therapeutically effective dose across the disclosed ranges would exceed the maximum tolerated dose in humans. Wyeth’s own witnesses agreed. Co-inventor Dr Haber accepted that the concentrations were “five times higher” than could be given to patients, and the inventors’ own 2008 publication had indicated this as well (p. 16).
However, the Federal Circuit was keen to stress that it was not ruling out all dose inventions lacking clinical data. Instead, it noted:
“We recognize that it is accepted practice … to claim a method of treatment disclosing a range of doses to be administered, without showing actual clinical data … The problem with these patents is that, perhaps because of close prior art, their claims are limited to dosage forms to be administered to patients, yet they disclosed only a broad range of doses some of which were shown to be toxic, and they disclosed no actual dosages for any compound within the scope of the claims, thereby leaving it to a practitioner … to perform undue experimentation.” (p. 19)
Teva v Eli Lilly and the trouble with routine
In Teva v Eli Lilly, decided earlier this year, the Federal Circuit reversed the district court’s judgment as a matter of law and reinstated a jury verdict that method of treatment claims to a whole genus of humanised anti-CGRP antagonist antibodies, with no sequence limitation, satisfied both written description and enablement (Evolve Insights). The reasoning was that such antibodies and the methods of making them were well known, that humanising them was routine, and that because all of them work in the claimed method, generating further members was “more akin to extra credit than a necessary research assignment”.
Comparing the two cases directly, in one a genus of unidentified antibodies was found enabled, whilst in another case a dose of one of three named small molecules was not. However, in Teva, the outstanding work for the skilled person was finding more members of a class every member of which was accepted to work. In Wyeth the question was whether any embodiment worked at all in the scope of the claim, with evidence indicating that some embodiments did not.
In Teva the Federal Circuit relied on the proposition that all humanised anti-CGRP antagonist antibodies treat headache, an assumption about the whole scope of a functionally defined genus on rather fewer worked examples than one might expect. In Wyeth the equivalent assumption, that a skilled oncologist can find a workable daily dose, was considered an assumption too far.
Analysis
Oddly, the message of these decisions appears to be that including more limitations and features in a claim can harm you from an enablement perspective, producing an enablement paradox. Adding in a feature may encourage the court to think about whether that feature is, in fact, enabled. Keeping a feature broader may conversely avoid scrutiny. The Teva case, for example, did not specify doses of the broad antibody genus to be used, but presumably a skilled person would have to work this out in addition to finding an effective antibody within the claimed genus. We wonder whether, if the patentee in Teva had specified a dose in the claims, the lack of enablement of a therapeutic dose for the claimed therapy would have been raised.
In light of these two cases, it seems we are now in a limbo with respect to how enablement will be tested by the USPTO. It remains to be seen whether examiners will take note of and be influenced by Teva and/or Wyeth.
Author: Rose Hughes
Rose is a biotech and pharmaceutical patent specialist with over a decade of experience in intellectual property. Rose is a patent attorney at Evolve, where she leverages our unique fractional in-house model to provide clients with deep patent law expertise combined with the strategic commercial oversight typically associated with senior in-house counsel.
With a PhD in Immunology from UCL, Rose applies her technical background to complex innovations in biologics, cell and gene therapies, and the rapidly emerging field of AI-assisted drug development. Previously, Rose held the role of Director. Patents at AstraZeneca, where she was responsible for global IP portfolios and IP strategy at every stage of the pharmaceutical pipeline, from platform development and on-market commercialization to SPCs and patent term extensions.
A recognized thought leader in the field, Rose has been a regular contributor to IPKat since 2018, offering practical insights into European patent law developments. She is also a frequent speaker on the epi podcast, a guest lecturer for the Brunel University IP law Postgrad Certificate, and a contributing author to published books A User’s Guide to Intellectual Property in Life Sciences (2021) and Developments and Directions in Intellectual Property Law (2023).
