Lack of enablement: A conclusion of lack of enablement means that the disclosure provided in the patent specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention, in this case without undue experimentation.
The US Court of Appeals for the Federal Circuit has found in Amgen v Sanofi and Regeneron that two of Amgen’s patents (US 882 9165 and US 885 9741), relating to the monoclonal antibody evolocumab and marketed by Amgen as Repatha ®, are invalid for lack of enablement. This is essentially because “undue experimentation” would be required to work the invention across the full scope of the claims. The decision upholds the decision of the lower District Court.
A copy of the decision can be found here: http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/20-1074.OPINION.2-11-2021_1731739.pdf
Repatha ® acts to bind and block the enzyme PKSK9, which regulates LDL (low density lipoprotein) receptor degradation. The action of the antibody allows LDL receptors to continue regulating the amount of LDL cholesterol circulating in the bloodstream, and elevated amounts of this cholesterol are linked to heart disease.
The issue before the court was whether or not the relevant claims satisfied the enablement requirement of 35 U.S.C. §112. The purpose of the enablement requirement is to ensure that the public is told how to carry out the invention i.e. to make and use it. Amgen’s claims defined antibodies in functional terms – essentially claiming any isolated monoclonal antibody which could bind one or more amino acid residues on the enzyme PCSK9, and also block binding of PKSK9 to LDL receptors. Amgen contended no undue experimentation was required to obtain antibodies fully within the scope of the claims, because of the “roadmap” antibodies provided in the specification, and because the skilled person could use well-known screening techniques or make conservative amino acid substitutions in the 26 antibody examples in the patent. In contrast, Sanofi argued that literally millions of antibodies were covered by the claims, the patents did not provide sufficient guidance, that antibody generation is unpredictable, and that substantial trial and error would be needed to practice the full scope of the claims.
After a review of the case law, including some commentary on the well-known Wands case (a key precedent setting out a number of factors to consider for enablement, and also relating to antibody technology), the court noted that the question of enablement for functional requirements can be particularly focused on the breadth of those requirements.In particular, it is important to consider the quantity of experimentation required to make and use, not only the limited number of embodiments in the patent, but also the full scope of the claim. It was noted, and applied in this case, that undue experimentation can include undue experimentation in identifying, from among the many identified compounds, those compounds that satisfy the functional requirement. In particular, it was noted that while functional claim limitations are not necessarily precluded, such limitations pose:
“high hurdles in fulfilling the enablement requirement for claims with broad functional language”.
Given that each appealed claim was a composition claim defined purely by functional limitations and not structure, the court held (agreeing with the District Court) that the specification did not enable preparation of the full scope of the double-function claims without undue experimentation. Indeed, it was noted that even the binding limitation itself was enough, in this case, to require undue experimentation.
The functional breadth of the claim was considered a particularly relevant factor. The court held that it was clear that the claims were far broader in functional diversity than the disclosed examples. It was noted that there were three claimed residues to which not one disclosed example binds, and that although the claims include antibodies that bind up to 16 residues, none of the patentee’s examples binds more than nine residues.
Another relevant factor with respect to satisfying the full scope of the functional limitations was considered to be the unpredictable nature of the antibody field. Evidence is needed that the full scope of broad claims can predictably be generated by the disclosed methods – evidence that was held to be lacking in this case. The court concluded that:
“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.”
It was further noted that the experimentation required to discover undisclosed claimed embodiments in this case would take a substantial amount of time and effort.
The decision is not necessarily unexpected, particularly given the breadth of the claims in issue, and it does appear to be broadly consistent with earlier decisions where broad claims covering a large “genus” of candidates (either in the chemical or biological field) have been considered. The present decision was specifically distinguished from the Wands case (in which the same court held broad claims to be allowable) on its facts, with the court noting that Wands does not hold that antibody screening never requires undue experimentation. However, it will be unwelcome news for patentees needing to enforce broad claims, particularly in the biological field. It is perhaps another reminder to patentees (and drafting attorneys) to avoid over-ambitious claiming and to ensure that, so far as possible, the disclosure is, as is often said, “commensurate with the scope of the claims”.
It seems unlikely that the US Supreme Court will hear any further appeal, given that it has not done so in similar cases where enablement of broad claims has been in issue. The present decision therefore looks likely to stand and may thus provide the leading guidance on enablement at the USPTO for some time to come.
Interestingly, Amgen’s corresponding European patent EP 2215124 was recently considered by the EPO Board of appeal in T845/19 (by video conference late in 2020). The European patent has been maintained in amended form, but only after significant limitation of the claims compared to the US patents. Thus, the allowed European claims include similar functional limitations to the US claims, but also define the antibody structurally in terms of specific light and heavy chain sequences, and also the CDR regions. This latest US decision may herald a further convergence of approach to the scope of antibody patents as between the US and Europe.