Key Points

• In Wyeth LLC v. AstraZeneca Pharmaceuticals LP, the Federal Circuit affirmed a District Court decision invalidating method claims as not enabled.
• The claims were directed to methods of treating certain cancers by daily administration of a pharmaceutical composition comprising a unit dosage of an EGFR inhibitor. Reference to “unit dosage” was interpreted as meaning a dose calculated to produce a therapeutic effect in a human patient.
• The decision discussed differences between patentability examination by the USPTO and regulatory evaluation by USFDA. In the end, the inclusion of particular language relating to dosing for human patients effectively raised the bar for the results that had to be achieved by the claimed methods — administration of the unit dosage had to kill cancer cells and be safe.
• The court found that the disclosure did not enable one of ordinary skill in the art to achieve those results without undue experimentation to identify an appropriate unit dose for daily administration.

The Federal Circuit recently upheld a District Court decision overturning a jury verdict that had found that Wyeth’s patent claims were not invalid and were infringed by AstraZeneca. In Wyeth LLC v. AstraZeneca Pharmaceuticals LP, the Federal Circuit’s analysis centered on the “unit dosage” claim feature, concluding that the specification did not enable one of ordinary skill in the art to identify a daily unit dose that provided a therapeutic effect — that is, was safe and effective — without undue experimentation.

This decision is important because although it acknowledges differences between patentability and regulatory approval standards, it shows how these standards may converge when the claim requires therapeutic treatment of a human patient.

Procedural History and Patents at Issue

The Wyeth patents at issue cover methods for using certain epidermal growth factor receptor (EGFR) inhibitors to treat drug-resistant non-small cell lung cancer. EGFR signaling pathways lead to cell proliferation, so inhibition of EGFR function can be used to prevent undesirable, cancer-causing cell growth. Wyeth sued AstraZeneca for induced infringement over its product, TAGRISSO® (osimertinib). AstraZeneca counterclaimed that Wyeth’s patents were invalid.

The patents asserted by Wyeth were U.S. Patent Nos. 10,603,314 (“the ’314 patent”) and 10,596,162, both issued in 2020. Claim 1 of the ‘314 patent is representative:

A method for treating gefitinib and/or erlotinib resistant non-small cell lung cancer in a patient in need thereof, comprising administering daily to the patient having gefitinib and/or erlotinib resistant non-small cell lung cancer a pharmaceutical composition comprising a unit dosage of an irreversible epidermal growth factor receptor (EGFR) inhibitor that covalently binds to cysteine 773 residue in the ligand-binding pocket of EGFR or cysteine 805 residue in the ligand-binding pocket of erb-B2.

The jury found that AstraZeneca failed to prove that the claims were invalid and that AstraZeneca had infringed the Wyeth patents, awarding Wyeth over $100 million in damages. Overturning the verdict, the District Court for the District of Delaware granted judgment as a matter of law (JMOL) that the asserted claims were invalid for lack of enablement and written description. Wyeth appealed.

Federal Circuit Decision

On appeal, the Federal Circuit affirmed the District Court’s decision invalidating the asserted claims on enablement grounds.

The court’s analysis of enablement focused on the claim feature “unit dosage.” “Unit dosage” was added to the claim during examination, apparently to overcome prior art by distinguishing the use of an irreversible inhibitor in a unit dosage form from “overdosing” with any inhibitor as described in a prior art reference. Under the enablement requirement of 35 U.S.C. § 112(a), the specification must teach one of ordinary skill to make and use the invention without undue experimentation. In interpreting the term, the Federal Circuit looked to the specification and concluded that the definition specifying a unit “containing a predetermined quantity of active material calculated to produce the desired therapeutic effect” meant that the unit dosage had to be suitable for providing a therapeutic effect in a human patient and thus must be both effective and safe. The court then concluded that there was insufficient information in the specification to enable one of skill in the art to identify a unit dosage for daily administration that would achieve that result without undue experimentation. There were no working examples and no methods for extrapolating doses from in vitro experiments in the specification. Perhaps more importantly, the only disclosed daily dose range of “from about 1 to 1000 mg, preferably from about 2 to 500 mg” included toxic, even potentially fatal, dosages.

While Wyeth contended that the district court’s approach improperly imported U.S. Food and Drug Administration (USFDA) safety requirements into the claim, the court rejected that argument and said they were simply using the language of the specification to interpret the term. In finding no error in the district court’s claim construction, the Federal Circuit stated that “[w]hile Wyeth is correct that the claims do not require FDA-type clinical safety or efficacy standards, it fails to appreciate and give meaning to other relevant claim terms—namely, that the claimed ‘unit dosage’ must be ‘administer[ed] daily’ to a human ‘patient.’…That interpretation does not import any FDA-type safety or efficacy requirements into the claims as Wyeth contends. It simply gives operative meaning to the claim language itself, which necessarily contemplates some repeatable dosing regimen calculated to produce a therapeutic effect in a patient.”

The decision also emphasized the importance of providing enabling disclosure in the specification and not relying only upon the knowledge of the person of ordinary skill in the art. The court stated: “Here, however, the specification leaves the determination of the claimed ‘unit dosage’ entirely to the knowledge of the skilled artisan. While the knowledge of one of ordinary skill may play an important role in enablement, it may not provide the only means to enable these specific claim limitations. That is what a specification of a patent must provide.”

An interesting aspect is that the preambles of the asserted claims refer to a “method of treating…in a patient.” Would the claims have been found enabled had they not contained “unit dosage”? In other words, would it be necessary to identify a specific dosage or dosing regimen in order to “treat a patient” with the EGFR inhibitor, given the safety issues? This was not explicitly addressed in the decision, as the court’s analysis relied on the daily administration of a unit dosage calculated to provide the therapeutic benefit.

Takeaways

The decision illustrates how adding dosing regimen or dosage limitations to claims can raise enablement issues. Broad claims in early applications can allow patentees to cover competing products, including structurally distinct products not even described in the specification. But when incorporating other limitations in the claims for patentability, there should be real meaning and workability behind those limitations. Ensuring that the specification provides operable embodiments or methods for identifying them can reduce the risk that the claims will be found invalid for lack of enablement.

The decision expressly recognizes the “accepted practice” that method-of-treatment claims, even those with dose limitations, do not require actual clinical data or evaluations of safety and efficacy at the level of the USFDA. The decision does not change that accepted practice. But it provides cautionary guidance for incorporating detailed aspects of therapeutic methods into claims, where, depending on the specific facts of the drug and the disclosure, the specification may fail to provide enough information to enable the entire scope of the claim.

Companies developing therapies to treat human disease often face difficult timing decisions when it comes to public disclosures and patent applications. Unable to sell their products without regulatory approval, they may file patent applications to cover disclosures being made during pre-clinical and clinical phases (with many of these disclosures being required in order to pursue regulatory approval). But in doing so, they may be filing without having the full picture of the product that will eventually be approved. Are all features of the claims fully described and enabled? Do they include embodiments that do not work? If a feature is to be determined by one of skill in the art, are relevant methods disclosed? Careful consideration should be paid to these questions in drafting the disclosure and in amending the claims during prosecution.

For more information, please contact Brooke Sargeant at 206.389.1503 or bsargeant@foxrothschild.com, or another member of Fox Rothschild’s national Intellectual Property Department.

This information is intended to inform firm clients and friends about legal developments, including the decisions of courts and administrative bodies. Nothing in this alert should be construed as legal advice or a legal opinion. Readers should not act upon the information contained in this alert without seeking the advice of legal counsel. Views expressed are those of the authors and not necessarily this law firm or its clients.