Federal Circuit Invalidity Determination for Idenix Underscores Continuing Intra-Circuit Split

One day before the now-famous Arthrex decision was issued, the U.S. Court of Appeals for the Federal Circuit (CAFC) decided an appeal by Idenix Pharmaceuticals LLC and Universita Degli Studi Di Cagliari (collectively “Idenix”) against Gilead Sciences, Inc. (Gilead) that reiterates the extent to which the Court is split in its approach to so many issues. The precedential opinion was authored by Chief Judge Prost, with Judge Newman dissenting.

In 2013, Idenix sued Gilead for infringement of U.S. Pat. No. 7,608,597 (the ‘597 patent), which claims a drug directed to the treatment of the hepatitis C virus (HCV). In response, Gilead argued that the ‘597 patent was invalid for failure to meet the written description and enablement requirements. At trial, the jury found for Idenix and upheld the validity of the patent. Gilead filed a renewed motion for Judgment as a Matter of Law (JMOL) on the written description and enablement requirements, and the court granted the motion only on enablement grounds, thus holding the patent invalid. The decision overturned the jury’s award to Idenix of $2.5 billion.

Analyzing the Claims

Reviewing the enablement requirement de novo, the CAFC also applied Third Circuit law to review the “factual underpinnings” of the evidence offered for enablement. The court turned to the claims of the ‘597 patent.

The key to the invention, argued Idenix, is the use of 2’-methyl-up nucleosides, such as nucleosides with the methyl group CH3 at the 2’ “up” position of a molecular sugar ring as shown. In response, Gilead argued that this description is overly broad because it does not name which 2’-methyl-up nucleosides are used in the invention to treat HCV. Further, Gilead argued that its product uses Fluorine (F) at the 2’-down position opposed to the hydroxyl group (OH) pictured here. Therefore, argued Gilead, because the ‘597 patent does not specify which 2’-methyl-up nucleosides were to be used (such as one with fluorine) the patent does not meet the enablement requirement.

Claim 1 of the patent recites the following:

1. A method for the treatment of a hepatitis C virus infection, comprising administering an effective amount of a purine or pyrimidine ?-D-2′-methylribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

The district court therefore found that while the claim requires methyl at the 2’-up position, no requirement is specified at the 2’-down position. The court also construed the preamble in combination with the requirement to administer an effective amount to limit the scope of the claims to treating HCV. The point of contention with enablement is therefore whether a person of ordinary skill in the art (POSITA), without undue experimentation, would know which 2’-methyl-up nucleosides would be effective for treating HCV.

Undue Experimentation Standard

Reviewing In re Wands, the CAFC analyzed the factors of undue experimentation, including: 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; 5) the nature and predictability of the field; 6) the level of ordinary skill; and 7) the scope of the claimed invention. The court stated that a finding of non-enablement was favored by a jury because “billions and billions” of compounds meet the claim limitations, making the scope overly broad. The ‘597 patent limits the substituent options at the 2’-up position to two dozen possibilities, but the court found that even where the patent is limited only to 2’-methyl-up variations, there are more than a dozen options at each of the R1, 2’-down, and the 3’-down positions. Additionally, the specification alone discloses 18 Formulas to determine 2’-methyl-up nucleosides that need to be tested for HCV treatment efficacy. With these factors combined, the CAFC held that undue experimentation would be required to narrow down the effective nucleosides.

Idenix argued that because the focus of the treatment is to inhibit NS5B polymerase, a POSITA would be aware of which nucleosides would be likely to accomplish this. Acknowledging this, the CAFC countered that the specification itself must also “supply the novel aspects of an invention in order to constitute adequate enablement,” opposed to sole reliance on the knowledge of a POSITA. Additionally, Idenix argued that considering the evidence the jury could have found that all 2’-methyl-up ribonucleosides would be effective in treating HCV, therefore the screening of each was irrelevant. The CAFC disagreed again, pointing out that Idenix’s own expert testified that “you don’t know whether or not a nucleoside will have activity against HCV until you make it and test it” and its counsel admitted that “not all 2’-methyl-up ribonucleosides will be effective to treat HCV.” The CAFC did however, acknowledge that a jury could have found that the synthesis of an individual compound was largely routine, and that a POSITA could synthesize this compound in relatively short order. Overall, however, the CAFC found that the evidence favored a finding of non-enablement.

Working Examples Must be Commensurate in Scope with the Claim

Idenix argued that the working examples in the ‘597 patent also weighed in favor of enablement, because the specification identifies the key modification (2’-methyl-up) paired with the active 2’-methyl-up ribonucleosides that were tested. The CAFC disagree here, stating that an enabling disclosure must be commensurate in scope with the claims which was not the case here. Claim 1, according to the CAFC, requires not only the identification of 2’-methyl-up but also which 2’-methyl-up nucleosides will treat HCV, and therefore the specification only provides a starting point and fails to provide proper guidance. Idenix argued that sufficient guidance is present because a POSITA would understand NS5B to be the target enzyme or would understand that the modified nucleoside must have a hydroxyl group or mimicking substitute at the 2’-down position. Again, the court reiterated that reliance on a POSITA is not enough to meet the enablement requirement, arguing specifically that requiring a POSITA “to engage in an iterative, trial-and-error process to practice the claimed invention” in the specification is not enough to show enablement. Additionally, even though the patent provides working examples, the court found that given the broad specification, four narrow examples of a single sugar ring are insufficient to support enablement. The court also held, based on trial testimony, that the art was unpredictable in nature and therefore favored non-enablement.

In affirming the district court’s finding of invalidity, the CAFC turned to Wyeth and Cordis Corp. v. Abbott Laboratories. The court argued that Wyeth is like the present case, in which both patents at issue consist of a claim encompassing millions of compounds made by varying the substituent groups, whereas only a small portion of those would actually have the claimed functional effects. The CAFC argued that because the court found the patent invalid for non-enablement in Wyeth, it must also do here too.

Denial of JMOL on Written Description

Lastly, to fulfill the written description requirement, patent owners “must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and demonstrate that by disclosure in the specification of the patent.” The CAFC likened this to “looking for blaze marks which single out particular trees in a forest, rather than simply pointing to trees. However, the CAFC argued, there were no specific blaze marks to direct a POSITA to the specific subset of 2’-methyl-up nucleosides that are effective at treating HCV. Furthermore, the court stated that the written description of a chemical invention requires a precise definition of the claimed subject matter to distinguish it from other materials. Finding that the ‘597 specification provides no way of distinguishing effective and ineffective compounds, the CAFC held that the ‘597 patent does not precisely define the claimed subject matter and thus does not meet the written description requirements.

Newman: The Jury Got it Right

Judge Newman disagreed with the majority. Specifically, she found the majority’s theory to be flawed with respect to 35 U.S.C. §112. She argued that a reasonable jury could have understood the claims to be directed to the nucleosides specifically described and shown to have the claimed antiviral activity.

My colleagues err in ruling that the claims cover ‘billions’ of variants. The ’597 specification recites a very large number of substituents for nucleosides that are not synthesized, not characterized, not evaluated, and not included in the claims. Some of these variants have been claimed in other patents and applications. However, they are not claimed in the ’597 patent. My colleagues err in holding that because other substituents and modifications are mentioned in the specification, claims that do not include such variants are invalid on grounds of indefiniteness and lack of written description.

As for the written description, Judge Newman contended that a reasonable jury could have found that the specification did not describe and enable products other than those whose properties were shown in the specification. Citing Tennant v. Peoria & P.U. Ry. Co., she argued that courts are not free to reweigh evidence and set aside jury verdicts solely because the jury could have drawn other inferences and the judge found those to be more reasonable.

There was substantial evidence that Gilead’s fluorinated product is not within the scope of the claims as they reasonably could have been viewed by the jury. The jury verdict of validity under section 112 is in accordance with law and supported by substantial evidence. I would decide this appeal on the ground that the claims, correctly construed, are valid and not infringed. From my colleagues’ contrary rulings, I respectfully dissent.

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