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Biogen v. Serano – When is a Recombinant Polypeptide Novel?

When I posted about this Fed. Cir. decision (Biogen MA v. EMD Serano, Appeal no. 2019-1133 (Fed. Cir., Sept. 28, 2020) on October 12, 2020, I viewed it as a straightforward application of the maxim that an otherwise non-novel product does not become novel by reciting method of preparation steps in the claims, e.g. that is “nested’ in the claims. Now, after reading Biogen’s petition for cert. filed in May 2021, I am not so sure that the Fed. Cir. decision is as simple as the panel would have us believe. The main claim of U.S. Pat. No. 7,588,755 reads, in part:

“A method for immunomodulating or treating a viral condition…comprising the step of administering to a patient…a therapeutically effective amount of a composition comprising:

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: DNA sequences which are capable of hybridizing to any of the inserts of…and which code for  a polypeptide displaying antiviral activity…”

Claim 3 limits the polypeptide to a single amino acid chain. This is a claim written to cover a method of medical treatment by administering an effective amount of human interferon- beta (hIFN-B) to treat MS. The use of hIFN-B derived from human tissue in small amounts to treat other viral afflictions was in the prior art. Thus, to avoid anticipation, Biogen had to convince the courts that the “recombinant polypeptide” it had obtained was novel over native (human) hIFN-B.

The district court judge found that the bioactivity of the recombinant polypeptide was due to its ability to fold similarly to the native hIFN-B, in effect arguing that the folded structure was an inherent claim limitation. It was not enough that the “core” amino acid sequence was in the prior art; defendants had to show that the bioactive native polypeptide was folded in a manner that was similar to the folded recombinant product—that similar folding was responsible for the bioactivity of the recombinant material. The district court also gave weight to expert testimony that the differences in the glycosylation of native hINF-B and the recombinant product would affect the “3D” folding to the extent that the two molecules were very similar in structure but not identical.

The biggest obstacle that Biogen had to overcome was the paucity of description of features of the recombinant polypeptide. The claims called for a recombinant polypeptide and “polypeptide” was defined in the patent as a “particular linear polypeptide sequence.” This is how the district court judge instructed the jury to read this term, and led the Fed. Cir. to conclude that, “for the purposes of this opinion, we refer to ‘recombinant INF-B as shorthand for the recombinant protein that meets these claims limitations.”

Apart from the panel’s use of the term “protein”, this finding effectively cut-off Biogen from arguing that the glycosylation (or absence thereof) in its recombinant product, or the inherent ability of the recombinant product to fold so as to remain bioactive. The patent specification has very little, if any, disclosure of the structural differences in glycosylation or the folding issue. Nonetheless, Biogen argued that the outcome of this case should be controlled by the Fed. Cir.’s decision in Amgen Inc. v. Hoffman-LaRoche Ltd., 580 F.3d 1340 (Fed. Cir. 2009) which found recombinant EPO not anticipated by “natural”  EPO derived from urine. But the Amgen claims go a lot farther in distinguishing the two products. One claim read:

“A non-naturally occurring glycoprotein product of the expression in a mammalian host cell of an exogenous DNA sequence encoding human [EPO] said process possessing [in vivo bioactivity].”

Here, the product is recited to be a “glycoprotein”, a claim limitation that is absent in the Biogen claim and one that positively recites glycosylation. The product is also recited to be “non-naturally occurring”, a term that is used in the present Biogen claim to describe the “host” but not the final product, e.g., the host could still produce human EPO. Amgen’s claim is limited to mammalian host cells, but it is clear that they produce a non-naturally occurring product. An analytical twist: If the Fed. Cir. legally strips off the glycosylation of the Biogen recombinant polypeptide, is it still anticipated by glycosylated native human INF-B? Maybe not, but the naked amino acid sequence is in the prior art (I assume) and would just lead Biogen from the frying pan into the fire. Also, is the Biogen product operable without any glycosylation?

This seems to be claim construction that is cut off from reality. The priority date of the patent is 1980(!), so reading both the patent and this opinion was a stroll down the heady memory lane of the dawn (or early morning) of the biotech industry. We will see if the S. Ct. helps Biogen continue the legacy.


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