By Cheryl Beise, J.D.
The district court properly found that the asserted patent is invalid for lack of enablement but erred in finding that the patent satisfied the written description requirement.
A patent owned by Idenix Pharmaceuticals claiming compositions and methods for treating the hepatitis C virus is invalid for lack of enablement and lack of written description, the U.S. Court of Appeals for the Federal Circuit has held. In setting aside a jury’s award of $2.54 billion in damages for willful infringement, the federal district court in Wilmington, Delaware, properly found that no reasonable jury could have found that the patent was not invalid for failure to meet the enablement requirement. The only conclusion supported by substantial evidence was that a person of skill in the art would have had to spend a great deal of time synthesizing a significant number of candidate compounds to practice the claimed invention. The district court, however, erred by not also finding that the patent was invalid for lack of written description. The specification provides no method for a person of ordinary skill in the art to distinguish effective from ineffective compounds (Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., October 30, 2019, Prost, S.).
In late 2013, Idenix Pharmaceuticals LLC and Universita Degli Studi di Cagliari (collectively, "Idenix") sued Gilead Sciences, Inc., for infringement of two patents for treating hepatitis C virus (HCV) infection. One patent was dropped from the suit. Based on the court’s claim construction, Gilead stipulated to infringement of the remaining patent—U.S. Patent No. 7,608,597 (the ’597 patent), entitled "Methods and Compositions for Treating Hepatitis C Virus," and the case proceeded to trial on the issues of willfulness, damages, and invalidity.
After a two-week trial in December 2016, the jury found that Gilead failed to prove that the asserted claims were invalid and awarded Idenix $2.54 billion in damages for Gilead’s willful infringement. The court entered judgment on the verdict. Both parties filed post-trial motions. The district court denied Idenix’s request for enhanced damages for willful infringement, higher ongoing royalty damages, and attorney fees. In February 2018, the district court granted Gilead’s judgment as a matter of law (JMOL), finding that no reasonable jury could conclude that the ’597 patent is not invalid for lack of enablement. The district court rejected Gilead’s argument that the patent also is invalid for lack of written description. Idenix and Gilead each appealed the adverse invalidity judgments.
The ’597 patent. The ’597 patent claims a method of treating HCV by administering nucleoside compounds having a specific chemical and stereochemical structure. At trial, Idenix asserted claims 1, 2, 4-7, 9-10, 16, 19, 23, and 28-31 of the '597 patent. Claim 1, the key independent claim, is directed to "A method for the treatment of a hepatitis C virus infection, comprising administering an effective amount of a purine or pyrimidine β-D-2’-methyl-ribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof."
The district court construed the structural limitation "β-D-2'-methyl-ribofuranosyl nucleoside" to require "a methyl group in the 2' up position and non-hydrogen substituents at the 2' down and 3' down positions." Claim 1, therefore, encompasses any β-D nucleoside meeting both the structural limitations (including a methyl group at 2'-up) and the functional limitations (efficacy in treating HCV). It is undisputed, however, that there are billions of potential 2'-methyl-up nucleosides. Neither party challenged the district court’s claim constructions on appeal.
Enablement. To satisfy the enablement requirement, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. The key enablement question in this case is whether a person of ordinary skill in the art would know, without undue experimentation, which 2'-methyl-up nucleosides would be effective for treating HCV.
In analyzing undue experimentation, the court considered the Wands factors: (1) the quantity of experimentation necessary; (2) how routine any necessary experimentation is in the relevant field; (3) whether the patent discloses specific working examples of the claimed invention; (4) the amount of guidance presented in the patent; (5) the nature and predictability of the field; (6) the level of ordinary skill; and (7) the scope of the claimed invention.
The Federal Circuit found that factor 1 favored a finding of non-enablement because the quantity of experimentation required to determine which 2'-methyl-up nucleosides meet claim 1 is very high. At trial, Gilead presented expert testimony that because the claim allows for nearly any substituent to be attached at any position (other than 2'-up), a person of ordinary skill in the art would understand that "billions and billions" of compounds literally meet the structural limitations of the claim. Idenix argued, a POSA would know to "take into account the patent as a whole" to focus on a "significantly smaller" set of candidate compounds. On the evidence presented, a reasonable jury at best could only have concluded that at least "many, many thousands" of candidate compounds exist. For largely the same reasons, factor 7, the scope of claims factor could only support a finding of nonenablement.
Factor 2 also weighed against a finding of non-enablement. The Federal Circuit also agreed with the district court's conclusion that while synthesis of an individual nucleoside was largely routine, a reasonable jury could only find that many candidate nucleosides would need to be synthesized before they could be screened, as not all candidate nucleosides were available for purchase.
The Federal Circuit noted that factors 3 and 4—relating to the presence of working examples and the amount of guidance presented—usually are analyzed together. Idenix argued that both factors weighed against non-enablement because the specification "identifies the ‘key’ modification (2'-methyl-up)" and contains working examples of active 2'-methyl-up ribonucleosides that were tested. The Federal Circuit disagreed. While it was true that the specification contains some data showing working examples of 2'-methyl-up nucleosides with efficacy against HCV, "four examples on a single sugar are insufficient to support enablement," particularly given the wide breadth of the claims at issue. Both factors 3 and 4 weighed against enablement. Factor 5 also weighed against enablement, according to the court, because based on the testimony presented at trial, "a reasonable jury could only have concluded that the use of modified nucleosides to treat HCV was an unpredictable art." Both parties’ experts testified at trial that the field was new and unpredictable.
Weighing the factors, the Federal Circuit concluded as a matter of law the’597 patent is invalid for lack of enablement. A reasonable jury could only have found that at least many, many thousands of 2'-methyl-up nucleosides meet the structural limitations of claim 1, not all of which are effective to treat HCV. Given the unpredictability of the art, and as admitted by Idenix, each of these compounds would need to be screened in order to know whether or not they are effective against HCV. Moreover, a significant number of candidate 2'-methyl-up nucleosides would need to be synthesized before they could be screened, which increases at least the quantity of experimentation required, even if the synthesis was routine. Finally, while the level of skill in the art is high, the ’597 patent does not provide enough meaningful guidance or working examples, across the full scope of the claim, to allow a POSA to determine which 2'-methyl-up nucleosides would or would not be effective against HCV without extensive screening. This immense breadth of screening can only be described as undue experimentation, the court said.
Written description. The core question posed by the written description requirement is whether the specification reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter. Gilead contended that the ’597 patent was invalid for lack of written description because the "closed, defined list of substituents at 2' (and 3') down" disclosed in the specification fails to describe the full scope of the claims, which includes all non-hydrogen substituents at these positions.
The parties disputed whether the specification demonstrates possession of the 2'-methyl-up 2'-fluoro-down nucleosides. There was no dispute that neither the ’597 patent nor any of its predecessor applications discloses a 2'-methyl-up 2'-fluoro-down nucleoside, including in any formulas or examples. Idenix argued instead that the claims are directed to the entire genus of 2'-methyl-up compounds for treating HCV, and are enabled by the disclosure of a number of examples. However, according to the court, the written description "fails to provide sufficient blaze marks to direct a POSA to the specific subset of 2'- methyl-up nucleosides that are effective in treating HCV."
The Federal Circuit acknowledged the principle articulated in Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340 (Fed. Cir. 2010) (en banc), that written description does not require "a nucleotide-by-nucleotide recitation of the entire genus," but this rule did not extend to this case, "where the specification lists tens or hundreds of thousands of possible nucleosides, substituent-by-substituent, with dozens of distinct stereochemical structures, and yet the compound in question is conspicuously absent." The absence of 2'-fluoro-down is conspicuous, according to the court. All seven formulas explicitly list fluorine as a possibility at other positions, including 2'-up. Yet not one of them includes fluorine at 2'-down, despite each listing more than a dozen possible substituents at that position. Further, to the extent Idenix argues that, although not disclosed, a POSA would have known to include fluorine at 2'-down based on its similarities to other halogens, that was insufficient for written description.
The Federal Circuit affirmed the district court’s judgment that the ’597 patent is invalid for lack of enablement and reversed the district court’s denial of judgment as a matter of law for failure to meet the written description requirement.
Dissenting opinion. Circuit Judge Pauline Newman filed a dissenting opinion to express her view that the majority erred in finding that the specific narrow claims of the ’597 patent are invalid. Judge Newman would uphold the jury’s patentability verdict. According to Judge Newman, a reasonable jury could have credited the evidence that the ’597 claims are for these specific compounds, not the "billions and billions" of unsynthesized and unevaluated variants in the specification. And a reasonable jury could have understood that subject matter that is unclaimed is irrelevant to validity under section 112. "I write in concern for the majority’s flawed theory of section 112, whereby the court requires description and enablement of the unclaimed and unsupported subject matter, in order to sustain validity of claims to the supported subject matter," Judge Newman said.
The case is No. 2018-1691.
Attorneys: Gregory A. Castanias (Jones Day) for Idenix Pharmaceuticals LLC and Universita Degli Studi Di Cagliari. E. Joshua Rosenkranz (Orrick, Herrington & Sutcliffe LLP) for Gilead Sciences Inc.
Companies: Idenix Pharmaceuticals LLC; Universita Degli Studi Di Cagliari; Gilead Sciences Inc.
MainStory: TopStory Patent FedCirNews
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