Innovators in the biotechnology and pharmaceutical sectors should take note of a decision issued by the U.S. court that hears appeals in patent cases. The court’s opinion in Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 1353 (Fed. Cir. 2011), points out some of the difficulties applicants face when drafting patent applications for inventions in “unpredictable” technologies involving biology and chemistry. We want to obtain broad claims for our clients. But when technologies are unpredictable, providing sufficient disclosure to describe and enable those broad claims can prove difficult. At the very least, we should strive to avoid placing any emphasis on unpredictable aspects of the invention when we draft an application. In Boston Scientific that did not happen, and as a consequence, claims in four patents were held invalid for lack of written description.

Johnson & Johnson, Inc. (“J&J”), and Cordis Corp. (“Cordis”) own U.S. Patent Nos. 7,217,286; 7,223,286; and 7,229,473 (collectively “the 1997 patents”) and, along with Wyeth, own U.S. Patent No. 7,300,662 (“the ’662 patent”) (collectively “the patents-in-suit”). These patents relate to drug-eluting stents for use in treating coronary artery disease (“CAD”). Bare metal stents, traditionally inserted in an artery to prevent collapse following angioplasty, did not adequately address restenosis (narrowing of the artery) caused by neointimal proliferation (an increase in smooth muscle cells of the artery over time in response to injury caused by angioplasty). Attempts to prevent restenosis led researchers to test numerous oral drugs and drug-eluting stents. Prior to 1997, orally administered rapamycin was known to inhibit restenosis in rats. Several analogs of rapamycin were also known in the art, including everolimus, which is both a macrocyclic lactone and triene analog of rapamycin. Cordis' Cypher® stent, which uses rapamycin as a therapeutic agent, was the first drug-eluting stent approved by the FDA and sold in the United States.

The 1997 patents, which share a common disclosure, claim drug-eluting stents using either “rapamycin, or a macrocyclic lactone analog of rapamycin” as the therapeutic agent. The 1997 patents contain only a single reference to “macrocyclic lactones” under the heading “Experiments,” but the experiments disclosed do not use or provide a single example of a macrocyclic lactone analog. 647 F.3d at 1358. Cordis added the phrase “macrocyclic lactone analog” in a 2006 claim amendment shortly after a competitor, Guidant, received European approval to sell a drug-eluting stent containing everolimus.

The ’662 patent claims drug-eluting stents using either “rapamycin or a macrocyclic triene analog of rapamycin,” but does not provide an example of a macrocyclic triene analog of rapamycin; rather, the only mention of a similar term in the specification is that “[r]apamycin is a macroyclic [sic] triene antibiotic.” Id. at 1359. The ’662 patent does not include any data on studies performed with any rapamycin analog coated stents. And, as with the 1997 patents, Cordis added the claim language “macrocyclic triene analogs” after Guidant received its European marketing approval.

Appellees Boston Scientific Corporation and Boston Scientific Scimed, Inc. (collectively “BSC”) filed four declaratory judgment complaints (later consolidated) against Appellants J&J, Cordis, and Wyeth alleging that the claims of the patents-in-suit are invalid. BSC sells an everolimus-eluting stent system in the United States. Appellants counterclaimed for infringement. The parties filed several motions for summary judgment in the district court, including BSC’s motion of invalidity based on nonenablement, lack of adequate written description, and indefiniteness. The district court granted summary judgment for BSC, finding the 1997 patents invalid for nonenablement and lack of written description, and the ’662 patent invalid for lack of written description without addressing enablement.

On appeal, the Federal Circuit agreed that the 1997 patents lacked an adequate written description of the claimed genus of macrocyclic lactone analogs of rapamycin. The shared specification contained virtually no information regarding the macrocyclic lactone analogs of rapamycin except that the term was mentioned under the heading “Experiments.” But not a single example disclosed use of a macrocyclic lactone analog. And the patents gave no guidance to a person of skill in the art on how to properly determine whether a compound was a macrocyclic lactone analog, given the potentially limitless number of compounds that are structurally similar to the complex rapamycin compound. Thus, the Federal Circuit held that “[a]n ipsis verbis disclosure of a claimed genus (under the heading Experiments) is not per se sufficient to meet the written description requirement.” Id. at 1364. In other words, merely naming a genus in a patent application without providing sufficient information to inform a person of skill in the art which molecules form part of the genus and which molecules do not is not enough to obtain valid claims to the broad genus.

The problems for the patent owner extended beyond the simple absence for the patent specification of disclosure sufficient to support the genus claims. Faced with the prospect of losing its patents because of the missing disclosure, the Appellants argued that the knowledge in the art was so well known as to excuse a more detailed disclosure in the specification. The Federal Circuit rejected this argument. While the court agreed that some species of the vast genus claimed were known in the art, Appellants’ own declarations (in response to attacks on the patents as being obvious over the prior art) detailed the failure of others to develop drug-eluting stents to inhibit restenosis and the unpredictability of the art.

Further, statements in the common specification indicated the uncertainties surrounding rapamycin, restenosis, and drug-eluting stents as of the effective filing dates of the patents. The patents stated that “[t]he exact hormonal and cellular processes promoting restenosis are still being determined,” and that “[t]he exact mechanism for restenosis is still under active investigation.” As for inhibitors of restenosis, the patents stated that “[t]he mechanisms for most agents employed [to prevent smooth muscle cell proliferation] are still unclear,” “[t]he ideal agent for restenosis has not yet been identified,” and “[t]he precise mechanism of rapamycin is still under active investigation.” Id. at 1365. The court stated that while a patentee may rely on information that is “well-known in the art” for purposes of meeting the written description requirement, “when the four corners of the specification directly contradict information that the patentee alleges is ‘well-known’ to a person of skill at the effective filing date, no reasonable jury could conclude that the patentee possessed the invention.” Id. at 1366-67.

Given the absence of information regarding the structural characteristics of macrocyclic lactone analogs or examples of macrocyclic lactone analogs in the specification, and the nascent state of using drug-eluting stents to inhibit restenosis, the court refused to “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.” Id. at 1367.

Addressing the ’662 patent, the Federal Circuit similarly found that the claimed subgenus of “macrocyclic triene analogs” of rapamycin was not adequately described. First, the court noted that the specification never disclosed the subgenus itself, that is, the specification never mentioned “macrocyclic triene analogs” of rapamycin; rather, the only disclosure was that “[r]apamycin is a macroyclic [sic] triene antibiotic.” Id. (alterations in original). As in Fujikawa v. Wattanasin, 93 F.3d 1559, 1570 (Fed. Cir. 1996), where a claimed subgenus was not disclosed ipsis verbis in the specification, the ’662 patent failed to indicate that the claimed triene analogs might be of special interest. Thus, the court found that given the nascent state of using drug-eluting stents at the time of filing, the lack of any “blaze marks” pointing to triene analogs precluded the conclusion that the analogs were adequately described.

Second, the Federal Circuit found that the functional disclosures in the ’662 patent failed to sufficiently describe the claimed subgenus of macrocyclic triene analogs or provide sufficient blaze marks as to which analogs might successfully work in drug-eluting stents. Even as of the 2001 effective filing date of the ’662 patent, the relationship between the function of rapamycin and its structure was not so well known that it excused the patentee’s failure to explicitly disclose the claimed subgenus or any species within the subgenus. Further, as with the 1997 patents, the ’662 patent confirmed that the mechanism of action of rapamycin was not well known in the art at the effective filing date, thus directly contradicting Appellants’ assertion that there was a well-known correlation between the structure of rapamycin and its function. According to the patent, “[i]t may be hypothesized that rapamycin acts to reduce negative remodeling in several ways. By specifically blocking proliferation of fibroblasts in the vascular wall in response to injury, rapamycin may reduce the formation of vascular scar tissue. Rapamycin may also affect the translation of key proteins involved in collagen formation or metabolism.” Id. at 1368. From this teaching, the court concluded that the mechanism of action corresponding to the function of rapamycin in preventing restenosis was still under investigation.

Would this case have been decided differently if the patents-in-suit had been better drafted? It is hard to say, but the uncertainty concerning the state of the art generated by the quoted passages from the patents clearly helped the court in concluding the claims were invalid. And, unfortunately for the patentees, those passages were entirely unnecessary. It is hard enough to obtain broad claims in the biological and chemical arts that fully comply with the written description (and enablement) requirements of Section 112, first paragraph. One should make the effort to ensure that the patent application itself does not make that goal more difficult by deleting statements from the application that an opponent might use to its advantage in arguing for the invalidity of your patent.