Amgen v. Sanofi and Regeneron – Enablement and the In re Wands Factors

On February 11, 2021, the Court of Appeals for the Federal Circuit (“Federal Circuit”) affirmed a district court’s judgment as a matter of law (“JMOL”) that Amgen’s asserted claims to binding affinity of antibodies were invalid for lack of enablement, holding that undue experimentation would be required to practice the invention claimed.

This case provides the Federal Circuit’s further guidance on the determination of enablement based on the factors provided in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), while such a determination based on the Wands factors still largely depends on factual analysis.

Amgen Inc. (hereinafter, “Amgen”) appealed from a decision of the District Court for the District of Delaware granting JMOL of lack of enablement of claims 19 and 29 of U.S. Patent 8,829,165 (the “‘165 patent”) and claim 7 of U.S. Patent 8,859,741 (the “‘741 patent”). These claims in the ‘165 patent and the ‘741 patent are directed to antibodies that bind to one or more of fifteen amino acid residues of a convertase enzyme, to interfere with the convertase enzyme (PKSK9)’s ability to remove receptors binding to low-density lipoprotein (“LDL”). These LDL receptors perform a function of removing LDL cholesterol from the bloodstream by binding to the LDL cholesterol. Therefore, blocking the convertase enzymes with the antibodies would have an effect on lowering LDL cholesterol. The court found that the claimed antibodies were defined by their function of binding affinity to specific amino acid residues on the PCSK9 enzyme and blocking the PCSK9/LDL receptor interaction. The specification was said to disclose amino acid sequences for twenty-six antibody species of the claims, including the antibody marketed by Amgen as Repatha®.

This case is the most recent case from the long procedural history since October 17, 2014, when Amgen filed suit against Sanofi, Aventisub LLC (collectively, “Sanofi”) alleging infringement of the ‘165 patent and the ‘741 patent.

The enablement requirement set forth in 35 U.S.C. §112 requires patent specifications to enable any person skilled in the art to make and use the patented invention. To prove that a claim is invalid for lack of enablement, a challenger must show by clear and convincing evidence that a person of ordinary skill in the art [1] would not have been able to practice the claimed invention [2] without undue experimentation. In determining the enablement, the Federal Circuit applies the Wands factors for guidance. The Wands factors provide guidance on the factual considerations that a court may consider when determining whether the amount of that experimentation is either undue for enablement or sufficiently routine such that an ordinarily skilled artisan would reasonably be expected to carry it out. The elements of the Wands factors are:

(1) the quantity of experimentation necessary,

(2) the amount of direction or guidance presented,

(3) the presence or absence of working examples,

(4) the nature of the invention,

(5) the state of the prior art,

(6) the relative skill of those in the art,

(7) the predictability or unpredictability of the art, and

(8) the breadth of the claims.

Here, in determining the breadth of the claims, the Federal Circuit found that the scope of the claims was indisputably broad. Instead of looking only at the number of possible embodiments falling within the claims, the court was “concerned with their functional breadth” and held that the claims are “far broader in functional diversity than disclosed examples” in the Specification.

In determining the predictability or unpredictability of the art, the nature of the invention, and the amount of direction or guidance presented, the Federal Circuit held that the invention is “in an unpredictable field of science with respect to satisfying the full scope of the functional limitations”. Based on the evidence, the Federal Circuit held that only “a small subset of examples of antibodies can predictably be generated.” The Federal Circuit found that “[h]ere, even assuming that the patent’s ‘roadmap’ provided guidance for making antibodies with binding properties similar to those of the working examples, no reasonable factfinder could conclude that there was adequate guidance beyond the narrow scope of the working examples that the patent’s ‘roadmap’ produced”, and that, after considering the disclosed roadmap for producing the claimed antibodies in view of the unpredictability of the art would lead a reasonable fact finder to conclude that the patent does not provide significant guidance or direction to a person of ordinary skill in the art.

In determining the quantity of experimentation necessary, the Federal Circuit also determined that obtaining the claimed embodiments outside the scope of the disclosed examples and guidance would take undue experimentation. A person having ordinary skill in the art could only do so through an involved trial and error process by making changes to the exemplary antibodies and screening for functionality or by discovering them via a randomization-and-screening roadmap.

In view of the Wand factors considered by the Federal Circuit, the court held that this process on the facts would have needed undue experimentation for a person of ordinary skill in the art to be able to practice the claimed invention and that the enablement requirement under § 112 is unmet, invaliding the claims at issue.

Since the In re Wands decision, the Federal Circuit began to discuss the full breadth of the claim in the context of enablement. This Federal Circuit’s decision will likely have an effect on claiming purely for antibodies’ binding affinity (functionality), as it may be practically challenging to provide a sufficient number of examples of antibodies to support enablement for the full breadth of a claim. The case is also a good reminder to avoid unreasonably broad claiming over the number of examples in the Specification and also to draft the Specification to include a broad base of examples, such that the disclosure is “commensurate with the scope of the claims” being claimed.