In Enzo Life Sciences v. Roche Molecular Systems, No. 2017-2498, 2017-2499, 2017-2545, 2017-2546, Slip op. (Fed. Cir. July 5, 2019), the Federal Circuit affirmed summary judgment of invalidity for lack of enablement of Enzo’s two patents relating to non-radioactive labeling of polynucleotides. The decision highlights non-enablement issues that may arise with respect to broad functional claims in an unpredictable field.

The Technology at Issue

A polynucleotide refers to a chain of nucleotides. Nucleotides are the building blocks of nucleic acids, generally known as DNA and RNA. Depending on the sequence of polynucleotides, two strands of polynucleotides can pair with each other, i.e., hybridize. Utilizing this concept, scientists can design a probe to detect the presence of certain nucleic acid sequences of interest.

For the probes to work, polynucleotides need to be labeled. For example, scientists have replaced certain atoms in the polynucleotides with radioactive isotopes. This is known as radioactive labeling. Non-radioactive labeling, on the other hand, was just developing at the time of the claimed inventions. Dr. David Ward, for example, demonstrated that attaching labels at certain positions of the nucleotide—e.g., a base position—would not disrupt the polynucleotide’s ability to hybridize and be detected upon hybridization. The patents-in-suit also involve non-radioactive labeling, but labeling at additional positions on a nucleotide—the “phosphate” position.

One patent, U.S. Patent No. 6,992,180 (“the ’180 patent”), relates to non-radioactive labeling of polynucleotides where the label is attached at the “phosphate” position of a nucleotide. The Federal Circuit characterized the claims as “quite broad” in scope, as they encompass all polynucleotides with labels attached to a phosphate. Slip op. at 11. Notably, the claims functionally require the polynucleotide to remain hybridizable and detectable upon hybridization. See id. at 5. The claims of the second patent, U.S. 8,097,405 (“the ’405 patent”), which also involves hybridization techniques using non-radioactively labeled probes, have an even “broader scope.” Id. at 16.

The Federal Circuit Affirms Non-Enablement

The district court had granted summary judgment holding that the asserted claims of the ’180 and ’405 patents are non-enabling. The Federal Circuit affirmed on appeal. The Court viewed the issue as whether the specification enables creation of a labeled probe that is both “hybridizable and detectable upon hybridization.” Slip op. at 9. The Court’s analysis was driven by “the functionality required by the claims.” Id. at 10.

The Court drew similarities to its earlier decision of non-enablement in Wyeth and Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380 (Fed. Cir. 2013). In Wyeth, the claims were broad and covered many compounds that required having an immunosuppressive functionality. But the patentee’s witnesses testified that minor alterations to the molecule disclosed in the specification could affect the immunosuppressive functionality. They also testified that one would need to first synthesize and test each compound to understand whether it would have the required immunosuppressive functionality. The Court in Wyeth thus concluded that there was no genuine dispute that practicing the full scope of the claims would require undue experimentation.

In this appeal, the Court also viewed the claims to be “quite broad,” as they “encompass all phosphate-labeled polynucleotides that are hybridizable and detectable” and do “not restrict the chemistry used to attach the label, the chemical linker used, the number of labels within a probe, or the location of the labels on the probe.” Slip op. at 11. Yet, the Court found, the specification does little to explain how these variables would or would not impact the claimed functionalities.

The Court also found that the art was “highly unpredictable,” making reliance on the knowledge of one of skill in the art insufficient for enabling disclosure. Id. at 13. Enzo’s expert testified that it was commonly thought that the addition of a non-radioactive label at positions other than a few known positions would interfere with or disrupt the hybridization process. According to Enzo’s expert, at the time of the claimed invention, therefore, “each labeled polynucleotide would need to be tested to determine whether it is hybridizable and detectable upon hybridization.” Id. at 14-15.

On this record, the Court concluded that “undue experimentation” would be required to practice the claims. Id. at 15. Thus, consistent with Wyeth, the Court held the claims to be non-enabling in view of the breadth of the claims, the unpredictability in the art, and Enzo’s expert testimony that each labeled polynucleotide would need to be tested to determine functionalities.