Federal Circuit's Expanding Application of the Written Description Requirement
By Kevin E. Noonan --
Last month, the Federal Circuit affirmed a District Court finding on summary judgment that claims relating to coronary artery stents coated with rapamycin analogs were invalid for failure to satisfy the written description requirement.
The technology relates to drug-eluting coronary artery stents, used to reduce restenosis after angioplasty. Rapamycin coating inhibits proliferation of arterial smooth muscle cells that caused the restenosis by a process called neointimal proliferation. Plaintiffs Johnson & Johnson, Cordis Corp., and Wyeth ("Johnson & Johnson) sold stents protected by U.S. Patent Nos. 7,217,286, 7,223,286, and 7,229,473 (collectively, "the 1997 patents") and U.S. Patent No. 7,300,662 (the '662 patent); the following claims are representative:
U.S. Patent No. 7,217,286
1. A device comprising a metallic stent, a biocompatible, nonabsorbable polymeric carrier, and a therapeutic agent, wherein: said polymeric carrier comprises an acrylate-based polymer or copolymer, a fluorinated polymer, or a mixture thereof, and said therapeutic agent is rapamycin, or a macrocyclic lactone analog thereof, and is present in an amount effective to inhibit neointimal proliferation.
2. The device according to claim 1 wherein said therapeutic agent is a macrocyclic lactone analog of rapamycin.
U.S. Patent No. 7,223,286
10. [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], wherein the coating comprises a lactone-based polyester; a lactone-based copolyester; a polyanhydride; a polyaminoacid; a polysaccharide; a polyphosphazene; a poly(ether-ester) copolymer; a polydimethylsiloxane; a poly(ethylene)vinylacetate; a poly(hydroxy)ethylmethylmethacrylate; an acrylate based polymer; an acrylate based copolymer; a polyvinyl pyrrolidone; a cellulose ester; a fluorinated polymer; or a blend thereof.
27. A stent according to any one of claims 1 to 26 wherein said drug is a macrocyclic lactone analog of rapamycin.
32. A stent according to any one of claims 1 to 26 wherein said rapamycin or macrocyclic lactone analog thereof is present in a therapeutically beneficial amount to inhibit neointimal proliferation.
33. A stent according to claim 32 wherein said drug is a macrocyclic lactone analog of rapamycin.
U.S. Patent No. 7,229,473
1. A metallic stent having a coating applied thereto, wherein: said coating comprises a mixture of a biocompatible polymeric carrier and a therapeutic agent; said polymeric carrier comprises at least one nonabsorbable polymer; said therapeutic agent is rapamycin, or a macrocyclic lactone analog thereof, present in an amount effective to inhibit neointimal proliferation; and said stent provides a controlled release of said therapeutic agent over a period of several weeks.
2. The metallic stent according to claim 1 wherein said therapeutic agent is a macrocyclic lactone analog of rapamycin.
U.S. Patent No. 7,300,662
1. A drug delivery device comprising: an intraluminal stent; a biocompatible, nonerodible polymeric coating affixed to the intraluminal stent; and from about 64 .mu.g to about 197 .mu.g of rapamycin or a macrocyclic triene analog thereof that binds FKBP12 incorporated into the polymeric coating, wherein said device provides an in-stent late loss in diameter at 12 months following implantation in a human of less than about 0.5 mm, as measured by quantitative coronary angiography.
13. A method of inhibiting neointimal proliferation in a coronary artery resulting from percutaneous transluminal coronary angioplasty comprising implanting in the lumen of said coronary artery a drug delivery device comprising: an intraluminal stent; a biocompatible, nonerodible polymeric coating affixed to the intraluminal stent; and from about 64 .mu.g to about 197 .mu.g of rapamycin or a macrocyclic triene analog thereof that binds FKBP12 incorporated into the polymeric coating, wherein said method provides a mean in-stent late loss in diameter in a human population at 12 months following implantation of less than about 0.5 mm, as measured by quantitative coronary angiography.
The District Court found the claims of each of the patents in suit to be invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112, 1st paragraph. In addition, the Court found the claims of the 1997 patents to be invalid for lacking an enabling disclosure. The patents claimed "rapamycin or a macrocyclic lactone analog of rapamycin" (the 1997 patents) or "a macrocyclic triene analog of rapamycin (the '662 patent). These portions of the molecule that can be derivatized are illustrated below. The District Court construed "macrocyclic lactone analog" and "macrocyclic triene analog" broadly to mean "any molecule with structural similarity to rapamycin."
The District Court relied on testimony and statements in the specification of the patents in suit that indicated there was no "clear path or direction towards a particular drug therapy for restenosis" at the time the invention was made. In addition, the specifications of the 1997 patents contained statements relevant to both the District Court's and the Federal Circuit's opinion regarding the state of (and knowledge in) the art at the time the applications were filed, including:
• "[n]umerous agents [that] are being actively studied as antiproliferative agents for use in restenosis and [that] have shown some activity in experimental animal models."
• rapamycin "is capable of inhibiting both the inflammatory response known to occur after arterial injury and stent implanta-tion, as well as the [smooth muscle cell] hyperproliferative response."
• "the precise mechanism of rapamycin is still under active investigation,"
• "the ideal agent for restenosis has not yet been identified."
The prior art disclosed some limited number (approximately 40) of rapamycin analogs known in the art, including the analog used by Boston Scientific's accused infringing product.
Regarding the '662 patent, rapamycin was defined to include "rapamycin, rapamycin analogs, derivatives and congeners that bind FKBP12 and possess the same pharmacologic properties as rapamycin." However, the '662 patent specification did not identify any specific rapamycin analogs, and did not define a "macrocyclic triene analog" or provide any examples. For both the 1997 patents and the '662 patent there were no teachings, disclosure or data of any species other than rapamycin.
The District Court granted summary judgment to Boston Scientific that the claims of the patents-in-suit were all invalid for failure to satisfy the written description requirement, and the claims of the 1997 patents were also invalid for lack of enablement. With regard to the 1997 patents, the Court found that the term "macrocyclic lactone analogs of rapamycin" "in no way restricts the universe of potential analogs fitting the limitations as construed by the court." The District Court also found that the specifications of the 1997 patents did not disclose any "definitions, examples, or experimental models . . . for determining whether a compound is a structurally similar analog as contemplated by the patentees." With regard to the ~40 rapamycin analogs known in the prior art, the Court noted that there were "numerous potential analogs of rapamycin," a number much greater than the ~40 known analogs. The District Court also found that merely specifying the required function of the rapamycin analog was insufficient to fulfill the written description requirement, because "describing certain functions of the genus of claimed analogs does not equate to a description of the claimed analogs themselves." The Court also relied on deposition testimony from the inventors that the had not experimented with any rapamycin analogs, saying that "[l]ogically, the inventors could not have described a knowledge that they did not possess."
The District Court distinguished the content of the '662 specification, recognizing that the scope of the rapamycin analogs was lower (limited to macrocyclic triene analogs) and the '662 patent specification provides more detail on the analogs and their properties, including mechanism of action. However, the Court found that this disclosure was also insufficient, because "[n]o 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." Even though the claimed genus is limited by function, there is no description of any species falling within the scope of the genus. As a consequence, the District Court found that the disclosure did not specify the "sufficient species" required by Federal Circuit precedent to fulfill the written description requirement. The Court thus "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.'"
The Federal Circuit affirmed in an opinion by Judge Moore, joined by Judge Bryson and by Judge Gajarsa with regard to the '662 patent. The opinion specifically rejected Johnson & Johnson's argument that the disclosure was sufficient based on the facts:
1) that the structure and the mechanism of action of rapamycin were known;
2) that the correlation between the structural elements of rapamycin and its mechanism of action and biological activity was known;
3) that dozens of rapamycin analogs having the same macrocyclic ring structure as rapamycin and comparable biological activity were known; and
4) 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.
Johnson & Johnson's argument was that the amount of the disclosure the patent specification was required to provide was reduced based on what was known in the art, citing In re Herschler, 591 F.2d 693, 702 (C.C.P.A. 1979), and In re Fuetterer, 319 F.2d 259 (C.C.P.A. 1963), for the principle that "when claiming a combination of known elements, as opposed to a novel compound, the specification 'need not list examples' nor is any 'comprehensive description' required." Johnson & Johnson also argued that the prior art contained "a known correlation between the structure of rapamycin and its analogs and their function," and hence Johnson & Johnson was entitled to its claims without having a specification that "contains examples of specific macrocyclic lactone analogs of rapamycin." In rejecting these arguments, the opinion expressed agreement with Boston Scientific's position that a patentee is required to show possession of the claimed invention at the time a patent application is filed, and that "[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," citing Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997). The 1997 patents fail this test, according to the Court, due to the complete absence of any examples of a macrocyclic lactone analog in the specification. Citing the en banc decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the opinion states 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." While disclaiming any "bright-line rules governing . . . the number of species that must be disclosed to describe a genus claim," the opinion reiterated the "factors" to be considered from Ariad: "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."
The specifications of the 1997 patents fail this test, containing "virtually no information regarding macrocyclic lactone analogs of rapamycin." Significantly, citing the absence of the term "macrocyclic lactone analog" until the claims were amended "nine years after the effective filing date," the opinion cites in detail the lack of disclosure relating to analogs. While not relying exclusively on the absence of any examples of macrocyclic lactone analogs in the specification, the opinion notes that such a lack of disclosure is a factor that "may be considered" when making a determination of whether the written description requirement is satisfied. In language reminiscent of how courts perform an enablement analysis, the opinion states that the 1997 patent specifications 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." The Court also recites the "structural complexity" of rapamycin (even going so far as enumerating the "fifty-one carbon atoms, seventy-nine hydrogen atoms, thirteen oxygen atoms and a nitrogen atom" comprising rapamycin). The opinion states that "the universe of potential compounds that are structurally similar to rapamycin and classifiable as macrocyclic lactones is potentially limitless" (and mentions the District Court's determination that "tens of thousands of potential macrocyclic lactone analogs [of rapamycin] exist"). Finally, the opinion states that "even the minor structural changes to the molecular structure of rapamycin that are necessary to create analogs may have significant and unpredictable effects on functionality," none of which were disclosed in the patent specifications.
The opinion discounts the existence of rapamycin analogs in the prior art, saying that "[a]ny suggestion that these references represented existing knowledge in the art so well known as to excuse including a more detailed disclosure of the macrocyclic lactone analogs genus in the specification is belied by the state of the art at the time of the invention." The patentees' own arguments (relating to non-obviousness) were turned against them in this regard, as the Court used the unpredictability associated with assertions of non-obviousness to establish that what was known in the art was insufficient to provide the knowledge of macrocyclic lactone analogs absent in the specifications. These arguments were also supported by statements in the 1997 patent specifications, including:
• "The exact hormonal and cellular processes promoting restenosis are still being determined."
• "The exact mechanism for restenosis is still under active investigation."
• "The mechanisms for most agents employed [to prevent smooth muscle cell proliferation] are still unclear."
• "The ideal agent for restenosis has not yet been identified."
• "The precise mechanism of rapa-mycin is still under active investigation."
The Federal Circuit expressly addressed the argument that there is (or should be) a distinction between claims directed to chemical compounds per se and claims (like the ones in suit) directed to a combination comprising chemical compounds. Citing Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., 541 F.3d. 1115, 1126 (Fed. Cir. 2008), the Court said that "our case law regarding generic claims is applicable to both inventions claiming novel genera of chemical and biological compounds as well as inventions claiming combinations of prior art compounds with other elements." "The test for written description is the same whether the claim is to a novel compound or a novel combination of known elements. The test is the same whether the claim element is essential or auxiliary to the invention," citing in support the statement in Aro Mfg. Co. v. Convertible Top Replacement Co., 365 U.S. 336, 345 (1961), that "there is no legally recognizable or protected 'essential' element, 'gist' or 'heart' of the invention in a combination patent."
Ultimately, the Court based its opinion on the knowledge in the prior art of a small subset of macrocyclic lactone analogs of rapamycin out of the "tens of thousands" of possible species, coupled with the failure to establish a correlation between the structure of such analogs and their function as restenosis inhibitors; in this regard the Court rebutted Johnson & Johnson's proffered expert evidence and a prior art article on rapamycin function with express statements in the 1997 patent specifications (such as "the precise mechanism of rapamycin is still under active investigation"; italics in opinion). Again echoing a traditional enablement analysis, the Court affirmed the District Court based on "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."
With regard to the '662 patent, while coming to the same ultimate conclusion, the Court acknowledged that this specification contained more information regarding the mechanism of rapamycin action than the specifications of the 1997 patents. Regardless, the Court notes that Johnson & Johnson's own experts admitted that "researchers continued to struggle to find compounds that would work in a drug-eluting stent to prevent restenosis," and thus "the technology was still in its infancy" at the effective filing date of the '662 patent. And the '662 patent "fails 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" recited in the '662 patent claims. Citing Fujikawa v. Wattanasin, 93 F.3d 1559, 1570 (Fed. Cir. 1996), the opinion holds that the '662 specification lacked sufficient "blaze marks . . . 'as to what compounds other than those disclosed as preferred, might be of special interest . . . simply describing a large genus of compounds is not sufficient to satisfy the written description requirement as to particular species or sub-genuses.'" In view of the "nascent state of using drug-eluting stents to treat restenosis" at the effective filing date of the '662 patent, the opinion states that the "lack of such blaze marks . . . prevents any conclusion that the patent contains sufficient written description of the claimed triene analogs of rapamycin." This conclusion was supported, according to the opinion, by the fact that the mechanism of action of rapamycin was not well known, and thus the knowledge in the art "did not excuse[] the patentee's failure to explicitly disclose the claimed sub-genus or any species within the sub-genus." As with the 1997 patents, the express disclosure of the '662 patent specification rebutted Johnson & Johnson's arguments regarding the sufficiency of its disclosure based on the knowledge of one of ordinary skill in the art, insofar as that disclosure indicated that "the mechanism of action corresponding to the function of rapamycin and its analogs [was] still under investigation." The '662 patent claims also suffered, according to the opinion, by the specific activity required by the expressly recited range of macrocyclic triene analogs, in view of the absence of any information (in the specification or the art) about how such analogs having such activity could be selected (other than "trial and error," again utilizing an enablement ("undue experimentation") analysis). Returning to written description, the opinion states that "[t]here is . . . no indication of which structural features of analogs of rapamycin are necessary to achieve these results."
Judge Gajarsa, perhaps reacting to the portions of the Court's analysis sounding in enablement, concurred in part because he would expressly affirm (regarding the 1997 patents) on enablement rather than written description grounds, saying that this portion of 112, 1st paragraph is "the appropriate tool for invalidating claims that are broader than their disclosure."
One explanation for the result in this case is that the 1997 patents, and even the '662 patent, were drafted at a time before the Federal Circuit's current emphasis on the written description requirement became fully evident. However, the opinion illustrates once again that the Federal Circuit is not cabining its written description jurisprudence to chemical, pharmaceutical, or biotechnological patents. In this case, the "invention" was the combination of the stent, which was known in the art, with compounds (rapamycin and analogs) that inhibited restenosis. Traditionally, the extent of the disclosure in the 1997 patents and the '662 patent regarding the restenosis-inhibiting compound might have been enough to satisfy the written description requirement; certainly disclosure of chemical genera has not been conventionally limited by the ratio of the species disclosed and the species in the genus, or no chemical specification could ever satisfy the requirement. After Ariad (and Carnegie Mellon), it is clear that the Court will apply its written description rubrics developed (sensibly) for biotechnology inventions (where the doctrine prevents applicants from claiming complex molecules that they have not yet isolated or identified) to more traditional chemical genera. The consequence, as here, is that claim scope will be limited, particularly for those claims drafted and granted prior to the sea change started by Regents v. Eli Lilly. Whether this stimulates or inhibits innovation in these technologies appears to be the legal and technological experiment that the Court will now have performed.
Boston Scientific Corp. v. Johnson & Johnson (Fed. Cir. 2011)
Panel: Circuit Judges Bryson, Gajarsa, and Moore
Opinion by Circuit Judge Moore; opinion concurring-in-part by Circuit Judge Gajarsa
Comments