Federal Circuit Finds Wyeth Restenosis Claims Invalid as Not Enabled

02 July 2013 PharmaPatents Blog

In Wyeth v. Abbott Laboratories, the Federal Circuit affirmed the district court’s decision that the claims at issue are invalid for failing to satisfy the enablement requirement of 35 USC § 112. The court took only 10 pages to explain why a specification that describes one specific compound did not enable claims encompassing tens of thousands of compounds.

The Patents at Issue

The patents at issue are U.S. Patent 5,516,781 and U.S. Patent 5,563,146, which are based on the same specification. As summarized by the Federal Circuit, the patents “relate to the use of rapamycin for the treatment and prevention of restenosis, which is the renarrowing of an artery.” The claims at issue recite methods of treating or preventing restenosis by “administering an antirestenosis effective amount of rapamycin” to a mammal.”

Important to this case, the term “rapamycin” may refer to a class of compounds. However, the patent specifications disclose only one rapamycin species, “sirolimus.” The structure of sirolimus includes a macrocyclic triene ring at C-1 to C-36 and a substituent group at and beyond C-37. position. As noted by the Federal Circuit, at the time the patent applications were filed it was known that sirolimus acts in part by binding two proteins at sites within the macrocyclic ring. It also was known that there were four additional compounds with the same macrocyclic ring as sirolimus, but different substituent groups beyond the C–37 position.

The patent specifications discuss the immunosuppressive and antirestenotic properties of sirolimus, and disclose “in vitro test data indicating that sirolimus inhibits rat smooth muscle cell proliferation,” and “in vivo test data indicating that intraperitoneal injection of sirolimus in rats reduced the thickening of the arterial wall following vascular injury.”

The District Court Proceedings

As summarized by the Federal Circuit, “[t]he defendants market stent products that elute everolimus and zotarolimus, two drugs that have the same macrocyclic ring as sirolimus but different substituents at the C–42 position.”

Wyeth urged a claim construction of “rapamycin” as “a compound containing a macrocyclic triene ring structure produced by Streptomyces hygroscopicus, having immunosuppressive and anti-restenotic effects.”

The district court adopted Wyeth’s construction, but held that the claims were not adequately described or enabled by the patent specifications. In so doing, the court noted that “the only species disclosed is sirolimus,” that the chemical arts are  unpredictable, that the invention is complex, and that there was limited knowledge of the treatment of restenosis using sirolimus at the time of the invention.

The Federal Circuit Decision

The Federal Circuit addressed only the enablement issue. It’s analysis begins with this succinct statement of the law:

A patent’s specification must describe the invention and “the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains . . . to make and use the same.” 35 U.S.C. § 112(a) (2012). Claims are not enabled when, at the effective filing date of the patent, one of ordinary skill in the art could not practice their full scope without undue experimentation. …. Enablement is a question of law based on underlying facts.

The Federal Circuit agreed with the district court’s finding that “practicing the full scope of the claims, measured at the time of filing, would require excessive experimentation” for two main reasons: (1) the scope of the claims in contrast with the guidance provided in the specification and (2) the burden of having to screen potential candidates for the required activity.

On the first point, the court noted that the claims encompass “at least tens of thousands of candidates,” but the only example in the specification is sirolimus. Further, “[t]he specification is silent about how to structurally modify sirolimus, let alone in a way that would preserve the recited utility. Indeed, the court noted that “it would be necessary to first synthesize and then screen each candidate compound using the assays disclosed in the specification to determine whether it has immunosuppressive and antirestenotic effects.” On this point, the court cited testimony from a Wyeth scientist to the effect that “‘until you test [compounds], you really can’t tell whether they work or not [i.e., have antirestenotic effects].’” Thus, the court found “no genuine dispute that practicing the full scope of the claims would require synthesizing and screening each of at least tens of thousands of compounds.”

On the second point, the court emphasized that even “routine experimentation is ‘not without bounds.’” The court characterized the specification as providing “only a starting point for further iterative research in an unpredictable and poorly understood field.” The court found that even “[s]ynthesizing candidate compounds derived from sirolimus could … require a complicated and lengthy series of experiments in synthetic organic chemistry,” and cited testimony from Wyeth’s expert that “it would take technicians weeks to complete each of these [functional] assays.” Thus, the court found “no genuine dispute that practicing the full scope of the claims, measured at the filing date, required undue experimentation.”

One Is Not Enough

It is not surprising that the Federal Circuit found that the disclosure of one compound with no other guidance was not enough to enable a broad genus, but this decision provides little guidance as to how many exemplary compounds or how much guidance might have been enough. Further, this decision indicates that even the need to carry out routine screening assays can undermine enablement when identifying compounds within the scope of the claims is akin to finding a needle in a haystack.

The recent change to a first-to-file patent system has placed a new emphasis on filing patent applications “early,” but this case warns that filing too early can backfire, particularly when broad claims are pursued.

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