In Goeddel v. Sugano, the Federal Circuit determined that a priority application that disclosed the gene encoding a full-length “precursor” protein did not constitute constructive reduction to practice of interference counts that focused on the “mature” protein. This decision is an important reminder that a disclosure that might be effective to render a claim obvious may nonetheless be ineffective to support a priority claim.
The protein at the center of this case is human fibroblast interferon (“hFIF”). The naturally occurring protein is produced in an inactive “precursor” form with 187 amino acids. The active “mature” form has 166 amino acids, and results from the cleavage of the N-terminal 21 amino acids (the “presequence” or “signal peptide”) of the precursor form.
The Interference Counts
There were two related interference proceedings: the “DNA Interference” and the “Protein Interference.” The subject matter of an interference is defined by the “count.”
The DNA Interference count was:
A DNA encoding a mature [hFIF] having a total of 166 amino acids of the sequence . . . . and unaccompanied by a [hFIF] presequence.
The Protein Interference count was:
A composition comprising water and a nonglycosylated mature [hFIF] polypeptide having a total of 166 amino acids and the following amino acid sequence . . . said composition being free of any glycosylated [hFIF].
The difference between the precursor protein and the mature protein was significant because “bacterial cells used in recombinant procedures could not reliably cleave the 21 amino acid presequence from the precursor hFIF.” Thus, it was recognized that DNA encoding the mature protein would be needed to express mature hFIF in bacterial hosts, such as E. coli.
Sugano’s Japanese Priority Application
Sugano’s Japanese priority application was directed to “a novel recombinant plasmid, having a gene which encompasses at least the entire coding region of the [hFIF] messenger RNA.” The application explained, “The ‘entire coding region’ means the part specifying the whole amino acid sequence of the protein of [hFIF] in the [hFIF] messenger RNA sequence.” A table in the application set forth the 187 amino acid sequence of the precursor form of the protein, without any identification of the presequence or mature sequence.
The application also stated:
It is important that in the sequence there exist without any errors the base sequence . . . corresponding to the amino acid sequence from the amino-terminal to the 13th amino acid of the [hFIF] reported in Knight et al. The fact proves that #319-13 plasmid has the [hFIF] mRNA sequence. Further, it is apparent from the data of the primary sequence that the plasmid encompasses the entire coding region of the protein of the above mRNA and probably the coding region of the signal peptide.
The Knight article identified the first 13 amino acids of the mature hFIF sequence.
The Board Decision
The Board of Patent Appeals and Interferences determined that Sugano’s Japanese priority application constituted a constructive reduction to practice of the counts, and so could serve as Sugano’s presumed date of invention. As set forth in 37 CFR § 41.201, a constructive reduction to practice requires “a described and enabled anticipation under 35 USC § 102(g)(1) in a patent application of the subject matter of a count.” Thus, underlying the Board’s award of priority was a determination that Sugano’s Japanese priority application adequately disclosed the “mature” hFIF DNA and protein of the counts in order to satisfy 35 USC § 112, first paragraph.
In particular, the Board determined that Knight’s disclosure of the first 13 amino acids of the mature protein would allow a person skilled in the art to identify the mature sequence in the precursor sequence that was set forth in the application. The Board cited expert testimony to the effect that the skilled artisan would have known how to “trim” the disclosed precursor DNA sequence in order to create a sequence that directly expressed the mature protein recited in the counts. All in all, the Board concluded that a skilled person could have “envisioned” the subject matter of the counts from the Japanese priority application, and so would have concluded that Sugano was “in possession of the invention of the interference counts.”
The Federal Circuit’s Reversal
On appeal, the Federal Circuit considered Goeddel’s arguments that Sugano’s Japanese priority application did not describe the subject matter of the counts. Goeddel pointed out that the application did not identify the presequence or mature sequence of the disclosed hFIF precursor protein, and did not describe any plasmids that express mature hFIF directly. Goeddel also cited expert testimony to the effect that the application did not characterize the disclosed protein as a precursor protein or include any discussion of the mature protein or signal peptide.
Sugano countered that the application, being directed to a person of skill in the art, did not need to “spell out every detail of the invention.” (Citing Lizard Tech., Inc. v. Earth Res. Mapping, Inc., 424 F.3d 1336, 1345 (Fed. Cir. 2005)) Sugano also argued that the citation to the Knight reference was sufficient to “convey” mature hFIF with “reasonable clarity” to a person of skill in the art. (Citing Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991))
Goeddel emphasized that regardless of what “could” have been understood from Knight, Sugano’s Japanese priority application simply failed to describe the subject matter of the counts—mature hFIF or DNA encoding mature hFIF without the presequence.
The Federal Circuit sided with Goeddel:
That a modified gene encoding the 166 amino acid protein could have been “envisioned” does not establish constructive reduction to practice of the modified gene. The question is not whether one skilled in this field . . . might have been able to produce mature hFIF by building upon the teachings of the Japanese Application, but rather whether that application “conveyed to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.”
Thus, the court reversed the award of priority to Sugano, and remanded the cases to the Board for further proceedings.
A Double Standard
This decision provides an example of a disclosure that might be effective to render a claim obvious but is not effective to support a priority claim.
Although the issue was not presented, it seems likely that if the Japanese priority application qualified as prior art, it would render the counts obvious. The application set forth the sequence of the precursor protein, Knight permitted identification of the mature protein in the precursor protein sequence, there was a recognized reason to be able to express the mature protein directly, and there was no question regarding enablement. Under KSR, these facts likely would support a determination of obviousness.
However, on the issue at hand—written description—the application fell short. In effect, by focusing on too much information—the full-length sequence—Sugano’s priority application did not include enough information on the shorter, mature protein.