Routine Experimentation Not Always Enough to Fend Off Enablement Challenge

On February 26, 2013, we analyzed Cephalon, Inc. et al. v. Watson Pharmaceuticals, Inc., where the Federal Circuit held that proving lack of enablement requires more than an expert saying it would be “complex” or “difficult.” The Federal Circuit’s unanimous decision in Wyeth v. Abbott Laboratories further clarified the enablement requirement and affirmed a lower court ruling that Wyeth’s patents covering the use of rapamycin are invalid for lack of enablement.

Wyeth’s patents at issue relate to the use of rapamycin to treat and prevent restenosis (renarrowing of the artery after a balloon catheter procedure). The claims outline a method of administering “…an antirestenosis effective amount of rapamycin to said mammal.” The specification includes data for only a single rapamycin species, sirolimus (a naturally occurring product).  The data demonstrated sirolimus’ immunosuppressive and antirestenotic properties. The main issue on appeal was whether practicing the full scope of the claims, which extended to all other species of rapamycin, would have required excessive – and thus undue – experimentation.

Wyeth argued that practicing the full scope would only require routine experimentation, and that a skilled artisan could (1) ascertain whether a candidate rapamycin compound has same macrocyclic ring as sirolimus and (2) determine if said compound has immunosuppressive and antirestenotic effects using the assays disclosed in the specifications. Wyeth’s expert also noted that one of ordinary skill in the art would have known two relevant facts that were absent from the specification. First, that in order to exhibit the desired function, the compound must be permeable across cell membranes. Second, such permeability typically occurs in compounds that have a molecular weight below 1,000 – 1,200 Daltons. Taken together, these facts significantly limit the universe of potential rapamycin compounds.

 The defendants argued that, even with these “limitations,” the universe of potential compounds would still require excessive experimentation since Wyeth conceded that even minor alterations to the sirolimus molecule could impact its immunosuppressive and antirestenotic properties. And even if this experimentation might be routine, it would still be unduly burdensome to have to run tens of thousands of potential compounds through screening assays to analyze the suitability of the compounds for use in the claimed invention.

 The Federal Circuit agreed with the defendants. The specification provided nothing more than “…a starting point for further iterative research in an unpredictable and poorly understood field.” Not only would the synthesis of these tens of thousands of compounds be challenging, but Wyeth’s own expert admitted that it would take technicians weeks to complete each assay. Further, the specifications offered zero guidance in the types of substitutions that could be made while preserving the activity seen in sirolimus. For these reasons, the resulting experimentation required is excessive.

 This case confirms the susceptibility of broad claims to an enablement challenge.  The Federal Circuit appears to be tightening the reins on the enablement requirement, and this decision may open the door for invalidity challenges to claims directed to large genera of compounds.  Even routine experimentation may not be sufficient to save a broad claim when performing that routine experimentation would be a very time-consuming and laborious process and the specification provides little guidance to help reduce that burden.