When is it undue experimentation in practicing the full scope of a claim that contains a genus of chemical compounds and a functional limitation of activity, when the specification provides a method to assess the claimed functional activity (and it can be routinely performed by one skilled in the art)? The Federal Circuit tackled this problem on Wednesday in the Wyeth v. Abbott Laboratories case, in which the Court affirmed a lower court's grant of summary judgment of non-enablement. It was unclear from the decision how many compounds were encompassed by this genus, but Abbott alleged that there were tens of thousands, and Wyeth's expert appeared to acknowledge that the number would be "significantly smaller" than "millions of compounds." Nevertheless, it was decisive to the Court that there were no suggestions in the patents at issue as to which substitutions in the compound would be preferable, that there was no guidance or predictions about any particular substitutions, and that the unpredictability in the art would have required the testing of each compound to see if it fell within the functional limitations of the claim. And, even though the Court acknowledged that undue experimentation is a matter of degree, synthesizing and screening tens of thousands of compounds qualified as "excessive" and therefore was found to be undue. The only other hint as to what amount of effort might or might not also qualify as "excessive" was that the Court noted that "it would take technicians weeks to complete each of these assays." Nevertheless, to affirm a grant of summary judgment with so many factual issues to consider, not the least of which was whether one skilled in the art would consider such experimentation to be undue, this was apparently not a close case for the Court.
As always, it is important to consider the claims at issue. The two patents were U.S. Patent Nos. 5,516,781 and 5,563,146, and claim 1 of the '781 patent is representative:
1. A method of treating restenosis in a mammal resulting from said mammal undergoing a percutaneous transluminal coronary angioplasty procedure which comprises administering an antirestenosis effective amount of rapamycin to said mammal orally, parenterally, intravascularly, intranasally, intrabronchially, transdermally, rectally, or via a vascular stent impregnated with rapamycin.
The technology at issue in this case was the use of balloon catheters to open blocked arteries, where the balloons are guided to the site of accumulated plaque and inflated to crush the plaque. However, such a procedure can cause injury to the arterial wall, resulting in the thickening of the walls, in a process known as restenosis. Therefore, treating restenosis is essentially a renarrowing of the artery. Rapamycin can refer to a class of compounds, but the patent only refers to a single species called sirolimus, which is naturally produced by a bacterium called Streptomyces hygroscopicus. Sirolimus is a macrocyclic triene ring, with the following structure:
This compound was known in the art, so the patents do not even contain this structure, instead referring to a patent that discloses and claims rapamycin (although again only the sirolimus compound). Nevertheless, even though the patents only refer to this one compound, the District Court adopted Wyeth's broad construction of "a compound containing a macrocyclic triene ring structure produced by Streptomyces hygroscopicus, having immunosuppressive and anti-restenotic effects." Therefore, any substituent beyond the C-37 position (the dashed circle) can be used to modify the structure and still fall within the scope of this definition. Wyeth likely sought such a construction because the defendants separately market stent products that elute everolimus and zotarolimus, which have the same macrocyclic ring, but different constituents at the C-42 position. The likely real problem that the Court had with this case, therefore, was that it appeared as if Wyeth was trying to assert its patents against currently used compounds that were not specifically taught in the patent disclosure (which itself only mentioned one species).
The enablement question turned on the fact that not all species of the rapamycin genus were immunosuppressive and anti-restenotic. Wyeth's expert did point out, however, that one skilled in the art would know that you could not just add anything to ring. If so, the number of possible species would be in the millions, and might approach infinite. However, to have the claimed functional effects, the compound would need to be permeable across cell membranes. This limits the practical size of compounds to below 1,000-1,200 Daltons (for comparison, sirolimus is approximately 914 Daltons). Even though there was some confusion at the oral hearing, the Court understood that this would limit the number of compounds to the tens of thousands. More importantly, because the patents in suit did not disclose any other species of this genus, there was no disclosure of which substituents would be preferable, or any predictions as to which substituents would be active. The only teaching along these lines was the inclusion of assays to determine immunosuppressive and anti-restenotic activity, which the Court accepted would be routine for one skilled in the art. Nevertheless, even though routine, testing tens of thousands of compounds would be excessive, and therefore the amount of experimentation was found to be undue.
The opinion was straightforward, and provides some guidance as to how many species of a generic compound could cause undue experimentation if the disclosure provides no guidance as to which substituents would fit the functional limitation. However, what was not clear from the opinion or the oral argument was whether one skilled in the art would have considered such testing to be undue, or at least whether this question should have been decided at trial. Also, it was unclear just how many species of the tens of thousands were, in fact, inoperative. It was suggested that only around seven had been identified as active, but no mention was made of the species that were found to be inactive. This could be because the Court believed this fact was irrelevant, especially in view of the unpredictability in the art. However, it would be interesting to know whether the decision would have been different if all known species were active. And, if so, what if only half of the species were active? The take home lesson is if you are drafting and prosecuting such claims, provide as much detail about the substituents as possible, and claim varying scopes of generic structures. Of course, Wyeth was stuck with its disclosure from 1992, and so they were between a rock and a hard place (because the defendants were not selling the species that they disclosed).
The really troubling aspect of this case came during oral argument, but did not make it into the opinion. This issue related to grant of summary judgment for lack of written description with regard to two routes of administration, specifically transdermally and rectally. Apparently, the inventors testified that they did not know how to administer the compound via these routes, and it was unclear whether anyone else in the art knew at the time. Judge Moore, who wrote the opinion, questioned from the bench whether the point of the written description requirement was to demonstrate that the inventor possessed the invention. And, if the inventor admits to not possessing a particular aspect of the invention, Judge Moore asked, can the specification truly be described? She then carried this line of thought to its logical, if not absurd, conclusion, that if a synthetic chemist does not know how to administer drugs to patients, how can they ever be entitled to method of treatment claims? She wondered if a formulator should also be included in the inventive entity, especially considering the fact that in this case both parties agreed that the definition of a person skilled in the art would also include a formulator. Of course, Wyeth's counsel cautioned against such draconian approach to pharmaceutical patent claims. Nevertheless, because the Court did not comment on the written description found in the specification, it is unclear whether Judge Moore was simply musing, or whether we can expect to see closer scrutiny of pharmaceutical method-of-treatment claims from her (or the Court in general), especially if such claims contain specific administration routes as limitations.
Wyeth v. Abbott Laboratories (Fed. Cir. 2013)
Panel: Circuit Judges Moore, Bryson, and Wallach
Opinion by Circuit Judge Moore