Issue(s): Was the district court correct in finding that the asserted claims of the the 1997 patents claiming drug-eluting stents are invalid for lack of adequate written description and lack of enablement claiming only “analogues” of rapamycin, and that the asserted claims of the ’662 patent are invalid for lack of adequate written description?
BOSTON SCIENTIFIC CORP. Plaintiffs-Appellees, v. JOHNSON & JOHNSON, CORDIS CORPORATION, AND WYETH, Defendants-Appellants. (2010-1230, -1231, -1233, -1234) Appeals from the United States District Court for the District of Delaware in consolidated case nos. 07-CV-0333, 07-CV-0348, 07-CV-0409, and 07-CV-0765, Judge Sue L. Robinson. (Decided: June 7, 2011). Before BRYSON, GAJARSA, and MOORE (author),
Facts: The patents-in-suit relate to drug-eluting coronary stents used in the treatment of coronary artery disease. Coronary artery disease is caused, in part, by atherosclerosis, a build-up of arterial plaque. Atherosclerosis limits the flow of blood and oxygen to the heart and can result in chest pain, blood clots, heart attacks, and other ailments.
In the 1980s, physicians began using bare metal coronary stents to support the artery after the physician deflates the balloon in balloon angioplasty. Although these bare metal coronary stents prevented the collapse of the artery and constriction due to scarring, restenosis remained a problem because the bare metal stents did not prevent neointimal proliferation.
Researchers experimented with drug-eluting stents in an effort to prevent restenosis. Researchers believed that the drugs contained on such stents could help prevent neointimal proliferation. In the early 1990s, researchers at Stanford University discovered that rapamycin inhibited restenosis after oral administration to rats. Cordis’s Cypher® stent was the first drug-eluting stent approved by FDA and sold in the United States. Cordis filed the application that issued as the ’662 patent in 2004, but asserts that the claims are entitled to an effective filing date of January 25, 2001. The ’662 patent defines rapamycin broadly to include “rapamycin, rapamycin analogs, derivatives and congeners that bind FKBP12 and possess the same pharmacologic properties as rapamycin.”
The 1997 patents claim drug-eluting stents using either rapamycin or a macrocyclic lactone analog of rapamycin as the therapeutic agent. The ’662 patent claims drug-eluting stents using either rapamycin or a macrocyclic triene analog of rapamycin. The rapamycin molecule has a number of structural features including lactone and triene moieties. Thus, rapamycin is both a macrocyclic triene and a macrocyclic lactone.
The 1997 patents share a common specification and generally claim drug-eluting stents utilizing “rapamycin, or a macrocyclic lactone analog thereof” as the therapeutic agent. Cordis first added the phrase “macrocyclic lactone analog” to the claims during an April 7, 2006 claim amendment during prosecution of the ’3286 patent. Cordis added these claims shortly after a competitor, Guidant, received European approval to sell a drug-eluting stent containing everolimus.
The 1997 patents indicate that rapamycin is of particular interest because it “is capable of inhibiting both the inflammatory response known to occur after arterial injury and stent implantation, as well as the [smooth muscle cell] hyperproliferative response.” However, the specification also states that “the precise mechanism of rapamycin is still under active investigation,”, and that “the ideal agent for restenosis has not yet been identified”.
The specification of the 1997 patents contains only a single reference to the claimed macrocyclic lactones. Under a subheading “Experiments,” the specification states, “Agents: Rapamycin (sirolimus) structural analogs (macrocyclic lactones) and inhibitors of cell-cycle progression.” The experiments disclosed under this subheading, however, only use rapamycin. The specification does not include any experiments using a macrocyclic lactone analog or even provide a single example of a macrocyclic lactone analog.
Unlike the 1997 patents where the shared specification mentions the genus (macrocyclic lactone analogs of rapamycin) and claims it in combination with other elements, here the inventors disclosed a genus (analogs of rapamycin), but claimed a narrower sub-genus of analogs (macrocyclic triene analogs of rapamycin) in combination with other elements. All of the data in the ’662 patent relate to studies done with rapamycin coated stents ─ there is no data on stents using any rapamycin analog. As with the 1997 patents, Cordis added claim language specifying “macrocyclic triene analogs” only after Guidant received approval for an everolimus coated stent.
Lower Court’s Disposition: Appellees Boston Scientific Corporation and Boston Scientific Scimed, Inc. (collectively, BSC), filed four complaints (later consolidated) against J&J and Cordis seeking declaratory judgments that the claims of the four patents-in-suit are invalid. (Claims 1, 2, 5, 6, 40, 41, 44, 47, and 48 of the ’3286 patent are not at issue in this appeal because the parties entered into a covenant not to sue). Boston Scientific Corp., 679 F. Supp. 2d at 542. BSC sells the accused Promus® Everolimus-Eluting Coronary Stent System (the Promus stent), which uses everolimus to prevent restenosis following implantation. The Promus stent is BSC’s private labeled version of Abbott Cardiovascular Systems Inc.’s (Abbott) XIENCE V® Everolimus-Eluting Coronary Stent System. Appellants previously asserted the patents-in-suit against Abbott in four civil actions in the District of New Jersey.
The district court granted summary judgment that the 1997 patents are invalid for nonenablement, and for failure to meet the written description requirement. Addressing written description, the district court determined that the 1997 patents disclose that the claimed analogs must have structural similarity to rapamycin (i.e., they must be macrocyclic lactones). However, the district court also noted that “this disclosure in no way restricts the universe of potential analogs fitting the limitations as construed by the court.”
The district court also determined that the specification fails to disclose any formulae or structures of any specific analog or provide any “definitions, examples, or experimental models . . . for determining whether a compound is a structurally similar analog as contemplated by the patentees.”
The district court next addressed the ’662 patent. In its claim construction order, the district court had construed “macrocyclic triene analog” to mean “a macrocyclic triene molecule with a structure similar to rapamycin and that binds FKBP12.” The district court determined that the ’662 patent gives more detail, as compared to the 1997 patents, regarding the mechanism of action of rapamycin. The district court found that, unlike the 1997 patents, “the ’662 patent explains that rapamycin binds FKBP12 which, in turn, binds to and inhibits the kinase TOR; this mechanism of action serves to inhibit neointimal hyperplasia and reduce restenosis.”
However, the district court further noted that: Notwithstanding the above disclosure, no macrocyclic triene analogs are named, structurally depicted, exemplified, or otherwise described in the ’662 patent specification. No assays or other experimental models are provided with respect to testing an analog candidate’s ability to function as rapamycin, that is, to bind FKBP12 which, in turn, binds to and inhibits the kinase TOR. . . . Thus, although limited by function, the claims of the ’662 patent are drawn to a genus of macrocyclic triene analogs without any description of any species within the genus.
The district court acknowledged that “some macrocyclic triene analogs were known in the art” but found that this “does not alleviate [Appellants’] obligation under § 112 to provide an example.” The district court concluded that “[t]he inventors were required to describe at least one representative macrocyclic triene analog; having failed to do so, the ’662 patent is [therefore] invalid for lack of written description.”
Findings on Appeal : “Compliance with the written description requirement is a question of fact but is amenable to summary judgment in cases where no reasonable fact finder could return a verdict for the non-moving party.” A specification adequately describes an invention when it “reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.”
The parties dispute whether the shared specification of the 1997 patents contains adequate written description regarding the claimed genus of macrocyclic lactone analogs of rapamycin. Appellants argue that the specification’s description of macrocyclic lactone analogs was sufficient to satisfy the written description requirement in light of the state of the art as of the effective filing date. Appellants contend that they submitted detailed evidence regarding the state of the art that precludes a finding on summary judgment.
Appellants contend that because information regarding the structure, mechanism of action, and biological activity of rapamycin and its analogs was set forth in the prior art, it was not necessary for the patent to disclose “formulae or structures” or set forth “definitions, examples, or experimental models” of particular macrocyclic lactone analogs. Instead, Appellants argue that the specification combined with the knowledge of one skilled in the art “provided a template for those of ordinary skill to use for identifying analogs falling within the scope of the claims.”
Appellants further contend that the prior art contained a known correlation between the structure of rapamycin and its analogs and their function. Appellants argue that because “functional claim language can meet the written description requirement when the art has established a correlation between structure and function,” Ariad, 598 F.3d at 1350, the specification does not need to contain examples of specific macrocyclic lactone analogs of rapamycin.
BSC argues that the specification of the 1997 patents fails to meet this test. BSC notes that there are no examples of “macrocyclic lactone analogs” of rapamycin in the patents. BSC also argues that the patents fail to disclose the structures or features that render a molecule sufficiently similar to rapamycin to classify it as a “macrocyclic lactone analog.” BSC contends that because the specification fails to disclose any of this essential information, there is nothing in the 1997 patents showing that the inventors possessed drug-eluting stents employing the broad genus of claimed macrocyclic lactone analogs. Additionally, BSC contends that upon consideration of “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,” Ariad, 598 F.3d 1359, the specification’s description of macrocyclic lactone analogs is insufficient.
We agree with BSC that no reasonable jury could conclude that there is sufficient written description support for the asserted claims of the 1997 patents. “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.”
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.”
Turning to the specification’s disclosure of macrocyclic lactone analogs of rapamycin, we agree with BSC 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.
Although examples are not always required to satisfy the written description requirement, the lack of any disclosure of examples may be considered when determining whether the claimed invention is adequately described. 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 (rapamycin contains fifty-one carbon atoms, seventy-nine hydrogen atoms, thirteen oxygen atoms and a nitrogen atom), the universe of potential compounds that are structurally similar to rapamycin and classifiable as macrocyclic lactones is potentially limitless.
At the effective filing date, very little knowledge existed regarding the use of drug-eluting stents to inhibit restenosis. In fact, Cordis’s Cypher® stent, which employs the patented technology, was the first drug-eluting stent marketed and approved in the United States. Appellants’ own expert declarations detail the failure of others to develop drug-eluting stents to inhibit restenosis and evidenced the “highly unexpected” and “remarkable clinical results seen in Cordis’s Cypher® stent.” Appellants also argued in their briefing in opposition to BSC’s § 103 summary judgment motion that the state of the art was highly unpredictable.
The shared specification indicates that the alleged correlation between structure and function was not well known by the effective filing date. Dr. Sabatini’s declaration explains that, based on the Choi article, rapamycin must first bind to FKBP12 via rapamycin’s pipecolinyl ring to form a rapamycin/FKBP12 complex in order to inhibit restenosis. Then this rapamycin/FKBP12 complex binds with mTOR. Id. Specifically, rapamycin’s triene group interacts with mTOR. Therefore, Dr. Sabatini’s declaration indicates that rapamycin’s structural features that allow it to function to inhibit restenosis are: 1) the pipecolinyl ring and 2) the triene group. However, the specification of the 1997 patents is silent about the need for the claimed analogs to maintain these two structural features.
Given the absence of information regarding structural characteristics of macrocyclic lactone analogs or examples of macrocyclic lactone analogs in the specification, the unpredictability of the art and the nascent state of using drug-eluting stents to inhibit restenosis, we affirm the district court’s grant of summary judgment. 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. Because we affirm the district court’s holding that no reasonable jury could conclude that the 1997 patents contained sufficient written description support, we need not separately address Appellants’ arguments regarding enablement.
GAJARSA, Circuit Judge, concurring-in-part: I agree with the majority that the asserted claims of U.S. Patents are invalid, but would hold the 1997 patents invalid for lack of enablement. The claimed invention is a combination of a stent, polymeric carrier, and therapeutic agent. The majority focuses solely on the written description aspect of whether the therapeutic agent’s analogs were adequately described and ignores that in nearly all of the asserted claims, the agents must effectively inhibit neointimal proliferation. Because undue experimentation was required to practice the 1997 patents, the district court’s grant of summary judgment of invalidity should have been affirmed on enablement grounds.
Allen’s Observations: The claimed invention is a classic device-drug combination, which is incredibly difficult to draft. Often such patent descriptions will recite Homeric catalogues of possible drugs to be used with possible device designs. Unfortunately, it appears that because drug-eluting stents were in their infancy, it was anyone’s guess which permutations would be medically and commercially viable. As such, written description and enablement become dicey for device-drug combinations. The only take home message is that, if possible, list all possible “analogues” as well as any functional assays to determine which of the drugs might have the desired effect.