In Boston Scientific Corp. v. Johnson & Johnson, the Federal Circuit affirmed the district court's determination that a series of stent patents are invalid for failing to satisfy the written description requirement of 35 USC § 112, first paragraph. The claims at issue recite stents that elute certain rapamycin "analogs," but the patents did not describe any specific analogs and were deemed invalid.
The Patents At Issue
The patents at issue (U.S. 7,217,286, U.S. 7,223,286, U.S. 7,229,473, and U.S. 7,300,662) are directed to "drug-eluting coronary stents used in the treatment of coronary artery disease." In particular, the patents relate to the use of rapamycin or macrocyclic lactone analogs thereof to prevent neointimal proliferation and restenosis (the re-narrowing of an artery after balloon angioplasty).
Claim 1 of the '3286 patent is representative:
1. A stent having a coating applied thereto, wherein said coating comprises a biocompatible polymer/drug mixture and said drug is rapamycin or a macrocyclic lactone analog thereof.
The '7286, '3286 and '473 patents all stem from a provisional application filed in 1997, and trace back to the first non-provisional application through a series of continuation applications (not continuation-in-part applications).
The '662 patent was filed in 2004, and claims priority as a continuation-in-part application to several applications filed in 2000 and 2001, and several provisional applications filed in 2000 and 2001.
The Written Description Issue
The Federal Circuit noted that "macrocyclic lactone analog" first was added to the claims in 2006, "shortly after a competitor, Guidant, received European approval to sell a drug-eluting stent containing everolimus."
The specification of the 1997 patents states that "[n]umerous agents are being actively studied as antiproliferative agents for use in restenosis and have shown some activity in experimental animal models," and includes "rapamycin" in a lengthy list. The specification also includes a more detailed discussion on rapamycin:
Rapamycin is a macrolide antibiotic which blocks IL-2-mediated T-cell proliferation and possesses antiinflammatory activity. While the precise mechanism of rapamycin is still under active investigation, rapamycin has been shown to prevent the G1 to S phase progression of T-cells through the cell cycle by inhibiting specific cell cyclins and cyclin-dependent protein kinases (Siekierka, Immunol. Res. 13: 110 116, 1994). The antiproliferative action of rapamycin is not limited to T-cells; Marx et al. (Circ Res 76:412 417, 1995) have demonstrated that rapamycin prevents proliferation of both rat and human SMC in vitro while Poon et al. have shown the rat, porcine, and human SMC migratin can also be inhibited by rapamycin (J Clin Invest 98: 2277 2283, 1996). Thus, rapamycin is capable of inhibiting both the inflammatory response known to occur after arterial injury and stent implantation, as well as the SMC hyperproliferative response. In fact, the combined effects of rapamycin have been demonstrated to result in a diminished SMC hyperproliferative response in a rat femoral artery graft model and in both rat and porcine arterial balloon injury models (Gregory et al., Transplantation 55:1409 1418, 1993; Gallo et al., in press, (1997)). These observations clearly support the potential use of rapamycin in the clinical setting of post-angioplasty restenosis.
On the other hand, the only mention of "analogs" is found under "Experiments," where rapamycin analogs are mentioned as possible "agents":
Agents: Rapamycin (sirolimus) structural analogs (macrocyclic lactones) and inhibitors of cell-cycle progression.
But, only rapamycin is actually mentioned in the (apparently prophetic) examples.
The specification of the '662 patent refers to rapamycin "analogs" in several places, but does not provide any definition, description, or examples of specific analogs.
The District Court Proceedings
Boston Scientific Corporation (BSC) sells the Promus® Everolimus-Eluting Coronary Stent System (the Promus stent), which uses everolimus to prevent restenosis following implantation. BSC sought declaratory judgments that the patents are invalid. Johnson & Johnson and Cordis pursued counterclaims of infringement.
The district court found that the 1997 patents were invalid for both lack of enablement and lack of written description under 35 USC § 112. The district court found that the '662 patent was invalid for lack of written description, but did not rule on enablement.
The Federal Circuit Decision
With regard to the 1997 patents, the Federal Circuit considered but rejected arguments that the "macrocyclic lactone analogs" were adequately described "in light of the state of the art as of the effective filing date."
The court considered evidence alleged to show:
- that the structure and the mechanism of action of rapamycin were known
- that the correlation between the structural elements of rapamycin and its mechanism of action and biological activity was known
- that dozens of rapamycin analogs having the same macrocyclic ring structure as rapamycin and comparable biological activity were known
- that persons of ordinary skill knew of assays to determine if analogs had the same mechanism of action as rapamycin and thus would also inhibit cell proliferation
But the Federal Circuit cited the following principles from Regents of the University of California v. Eli Lilly & Co.:
A written description of an invention involving a chemical genus, like a description of a chemical species, “requires a precise definition, such as by structure, formula, [or] chemical name,” of the claimed subject matter sufficient to distinguish it from other materials.
and Ariad Pharmaceuticals., Inc. v. Eli Lilly & Co.:
We have “held that a sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.”
The court acknowledged its discussion in Ariad to the effect that satisfaction of the written description requirement depends on "a number of factors," such as "'the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.'" but found that "no reasonable jury could conclude that the inventor possessed the claimed subject matter."
"The shared specification of the 1997 patents contains virtually no information regarding macrocyclic lactone analogs of rapamycin"
Reciting a litany of shortcomings, the Federal Circuit noted:
The 1997 patents contain no examples of macrocyclic lactone analogs of rapamycin, and give no guidance on how to properly determine whether a compound is a macrocyclic lactone analog of rapamycin besides vaguely indicating they must be 'structural[ly] similar' to rapamycin. Given the structural complexity of rapamycin . . . the universe of potential compounds that are structurally similar to rapamycin and classifiable as macrocyclic lactones is potentially limitless. As noted by the district court, the Appellants do not specifically contest that tens of thousands of potential macrocyclic lactone analogs exist.
The court also found that in 1997 "very little knowledge existed regarding the use of drug-eluting stents to inhibit restenosis," and that the specification itself acknowledged uncertainty and unpredictability in this field. The court concluded:
"The patent laws do not reward an inventor’s invitation to other researchers to discover which of the thousands of macrocyclic lactone analogs of rapamycin could conceivably work in a drug-eluting stent."
Although the '662 patent was filed several years later, it did not fare better in the court's analysis. The court determined that the field of the invention "was still in its infancy" and that the '662 patent likewise failed "to disclose even a single member of either the genus of 'analogs' of rapamycin, or the more specific genus of 'macrocyclic triene analogs' of rapamycin.
The Federal Circuit therefore affirmed the judgment of invalidity of all patents for lack of written description.
Judge Gajarsa's Concurring Opinion
Judge Gajarsa wrote a separate opinion concurring-in-part with the majority. In particular, Judge Gajarsa would have invalidated the 1997 patents for lack of enablement, not lack of written description.
The enablement requirement of 35 U.S.C. § 112 ¶ 1 is the appropriate tool for invalidating claims that are broader than their disclosure. The majority blurs the line between enablement and written description ....
On the other hand, Judge Gajarsa joined the majority opinion with regard to the '662 patent, apparently because its specification does not include express support for "macrocyclic triene analogs" of rapamycin.
A Bright Line?
Although the Federal Circuit was careful not to draw a bright line here, and did not hold that a lack of even one specific example necessarily fails to satisfy the written description requirement, its recent written description jurisprudence seems to be heading in that direction. In my experience, USPTO examiners are reluctant to allow claims directed to unspecified "analogs" or "variants," so this battle often is fought during examination. Still, the court appears to leave room for circumstances where the state of the art is such that unspecified "analogs" may be adequately described and enabled.