October 30, 2019

Synthesizing and Screening Thousands of Candidate Compounds Constitutes Undue Experimentation

In Idenix Pharmaceuticals LLC. v. Gilead Sciences Inc., [2018-1691] (October 30, 2019), the Federal Circuit affirmed that U.S. Patent No. 7,608,597 was invalid for lack of enablement, and further held that it was invalid for lack of written description, as well.

In 2016, a jury found the patent was valid and awarded damages. Gilead filed a motion for JMOL, which was granted as to enablement but denied as to written description.

The only independent claim of the ’597 patent recites:

  1. A method for the treatment of a hepatitis C virus infection, comprising administering an effective amount of a purine or pyrimidine β-D-2′-methylribofuranosyl 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,” while construing the preamble “[a] method for the treatment of a hepatitis C virus infection,” as a narrowing functional limitation, limiting the scope to the set of compounds that are effective for treatment of HCV.

The Federal Circuit observed that while the claim requires methyl at the 2′-up position, it allows nearly any imaginable substituent at the 2′-down position. It was undisputed that there are billions of potential 2′-methyl-up nucleosides. The key enablement question was 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. The Federal Circuit concluded they would not.

The Federal Circuit agreed with the district court that the quantity of experimentation required to determine which 2′-methyl-up nucleosides meet claim 1 was very high, favoring a finding of non-enablement. Even taking into account that a person of ordinary skill would know to eliminate certain substitutes, there was still a large number of possibilities. Even just testing the compounds expressly listed in the specification would require considerable effort.

The Federal Circuit further found that there was insufficient guidance in the specification as to which the 2′-methyl-up nucleosides will effectively treat HCV, stating that without specific guidance on that point, the specification provides “only a starting point, a direction for further research.” It is not enough to identify a “target” to be the subject of future testing. A specification that re-quires a POSA to “engage in an iterative, trial-and-error process to practice the claimed invention” does not provide an enabling disclosure.

The unpredictability of the art, and the broad scope of the claims, weighed in favor of non-enablement.

Weighing each of the Wands factors, the Federal Circuit concluded as a matter of law that the ’597 patent is invalid for lack of enablement. Having to synthesize and screen each of at least tens of thousands of candidate compounds constitutes undue experimentation.

On the issue of written description, the Federal Circuit said that to fulfill the written description requirement, a patent owner 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.

In the context of the this case, this meant that the patent must demonstrate that the inventor was in possession of those 2′-methyl-up nucleosides that fall within the boundaries of the claim (i.e., are effective against HCV), but are not encompassed by the explicit formulas or examples provided in the specification.

A genus can be sufficiently disclosed by 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, which the Federal Circuit has described as “looking for blaze marks which single out particular trees” in a forest, rather than simply “pointing to trees.”

In particular the Federal Circuit noted the conspicuous absence of any disclosure of the accused compound, saying that a POSA would not “visualize or recognize the members of the genus” as including the accused compound, and thus the specification could not demonstrate to a POSA that the inventor had possession of that embodiment at the time of filing.