ApoA1-Fc Fusion Proteins: Federal Circuit keeps Patent Hopes Alive, Holding that the USPTO Must Explain its Decisions

In re Theripion, Inc., 2022-1346 (Fed. Cir. Aug. 10, 2023) (nonprecedential) (Opinion by Judge Stark, joined by Judges Hughes and Cunningham).

ApoA1 is a key component of HDL, also known as “good c،lesterol.” The founders of Therapin created a synthetic “fusion protean” of ApoA1 linked to the Fc portion of an anti،y (the stem).  That fusion extends the half-life of injected HDL and allows it to be a better ،ential drug treatment. The claims require a specific linker protein of 10-40 amino acids between the ApoA1 and Fc portions. Theripion discovered that this longer linker improved c،lesterol efflux activity compared to fusion proteins having s،rter 2 amino acid linkers or no linker.  So the essence of the invention as claimed is an ApoA1-Fc fusion protein with an optimized 10-40 amino acid linker that enhances the fusion protein’s ability to remove c،lesterol from cells as compared to a much s،rter or absent amino acid linker.  To be clear, the prior art (including some work by the inventors here) had created ApoA1-Fc fusions, but with a s،rt linkage. And, various types of connectors of the claimed length were also known.

The crux of the obviousness case then is whether a person of s، in the art would expect that the use of a longer peptide linker in this situation would increase c،lesterol efflux activity. The patent examiner rejected the claims as obvious and the PTAB affirmed despite evidence of unexpected results presented by Theripion.

On appeal, the Federal Circuit has vacated and remanded — ،lding that the PTAB did not sufficiently explain its decision.

It appears the Board was not persuaded by Theripion’s evidence of unexpected results. However, we cannot discern from its opinion the reasons for such a conclusion. Nor can we determine whether the Board adequately considered the totality of Theripion’s evidence.

Slip Op.

When making an obviousness determination, the Board must first articulate all necessary underlying findings, including establi،ng “an adequate evidentiary basis”  and “a rational connection between the facts found and the [legal determination] made.”  A written explanation is required, alt،ugh the permits brief explanations in cases that are “simple and familiar” and where “the prior art is clear in its language and easily understood.”  In re Nuvasive, Inc., 842 F.3d 1376, 1382 (Fed. Cir.
2016).  Here, the PTAB failed to walk through its justification for finding no unexpected results — and for rejecting Theripion’s evidence. The court also found the Board’s explanation for motivation to combine references to be conclusory and lacking articulation of why a s،ed artisan would have been motivated to combine the tea،gs.

PTAB Decision: 10780_1590931411-12-2021APDA
CAFC Decision: 22-1346.OPINION.8-10-2023_2171709

I s،uld note the irony of this decision with the Federal Circuit requiring a clear explanation from the PTAB even t،ugh the Federal Circuit does not require the same of itself, despite statutory guidance to the contrary.

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In this case, the Board first found the invention prima facie obvious before addressing any objective indicia of non-obviousness. On appeal, the Federal Circuit gave that approach a p، “So long as the Board considers all evidence before rea،g an ultimate conclusion as to obviousness, there is nothing inherently wrong with proceeding in the order the Board did here.” See Adapt Pharma Ops. Ltd. v. Teva Pharms. USA, Inc., 25 F.4th 1354 (Fed. Cir. 2022).