In a case relating to use of recombinant human interferon-β (IFN-β) proteins for the treatment of viral diseases, the US Court of Appeals for the Federal Circuit ruled that a “product-by-process” analysis applies even when the product-by-process limitation is nested within a method of treatment claim. Biogen MA Inc. v. EMD Serono, Inc., et al., Case No. 19-1133 (Fed. Cir. Sept. 28, 2020) (Linn, J.).

The claims at issue relate to a method of treating a viral condition, a viral disease, cancers or tumors by administration of a pharmaceutically effective amount of recombinant IFN-β. The claims contained a product-by-process limitation that partially defined the recombinant IFN-β in terms of the method or process by which it is made:

a recombinant polypeptide produced by a non-human host transformed by a recombinant DNA molecule comprising a DNA sequence selected from the group consisting of . . .

It was undisputed that native IFN-β proteins comprise sequences identical to those recited in the claims at issue, and that native IFN-β had been used in the prior art to treat viral conditions. At issue was whether the use of native IFN-β to treat viral conditions anticipated the use of recombinantly produced IFN-β for the claimed treatment.

When considering product-by-process claims, the Federal Circuit has long held that “an old product is not patentable even if it is made by a new process.” See, e.g., Amgen v. Hoffmann-La Roche (Fed. Cir. 2009). The district court granted Biogen’s judgment as a matter of law (JMOL) motion and reversed the jury verdict on anticipation, reasoning that the Amgen analysis did not apply here because the claims were directed to a method of treatment and not a product. Further, the “source limitations” (i.e., the limitations requiring that the IFN-β be produced using recombinant methods) overcame the shortcoming of the prior art. Namely, the unavailability of native IFN-β in sufficient quantity to facilitate practical treatment “lies at the heart of the benefit of this invention” and should be given “force and effect in the anticipation analysis.” Serono appealed.

The Federal Circuit reversed, explaining that the nesting of the product-by-process limitation within a method of treatment claim does not change the proper construction of the product-by-process limitation itself. The Federal Circuit reasoned that “an old method of administration of an old product made by a new process is not novel and cannot be patented.” Further, the Court found that the district court erred in considering the advantages of the recombinant process—the new capability of manufacturing sufficient quantities of IFN-β through recombinant technology—as a reason not to apply the product-by-process analysis. The proper anticipation analysis does not turn on the source of the claimed polypeptide, but on a comparison of the claimed recombinant polypeptide and the prior art native polypeptide.

In granting JMOL, the district court alternatively reasoned that under a product-by-process analysis, the native IFN-β could not anticipate recombinant IFN-β, because the prior art did not disclose that the native and recombinant IFN-β shared an identical three-dimensional structure or that the native IFN-β would not necessarily demonstrate “antiviral activity” when administered in a “therapeutically effective amount” as recited by the claims.

The Federal Circuit found this reasoning flawed:

• First, the Biogen patent explicitly defined “polypeptide” as “a linear array of amino acids” without regard to its folded protein structure, and in fact, the district court charged the jury with this definition. Biogen did not dispute the fact that the “sequential order of the amino acid residues for the native IFN-β is the same as the sequential order of the amino acid residues for recombinant IFN-β.”

• Second, in calling for antiviral activity, the claims do not recite any specific folded three-dimensional structure that gives rise to that activity. The claimed antiviral activity could arise from the administration of any three-dimensional protein with a linear amino acid sequence identical to the claimed recombinant “polypeptide.”

• Finally, Biogen did not ask for a jury instruction on anticipation that required comparing the three-dimensional protein structures of the prior art IFN-β and the claimed recombinant IFN-β, nor did it object to the jury’s instruction to decide anticipation based on the linear amino acid sequence.

Accordingly, the Federal Circuit reversed the district court’s grant of JMOL of no anticipation and the conditional grant of a new trial on anticipation, and ordered reinstatement of the jury verdict of anticipation.