Earlier today, the Federal Circuit reversed the Final Written Decision, and reconsideration of that decision, by the U.S. Patent and Trademark Office Patent Trial and Appeal Board, which determined that claims 1-24 of U.S. Patent No. 8,952,138 were unpatentable under 35 U.S.C. § 103(a).

The '138 patent is directed to methods for refolding proteins at high concentrations using a controlled reduction-oxidation (redox) reaction.  Claim 1, the lone independent claim, is set forth below:

1.  A method of refolding a protein expressed in a non-mammalian expression system and present in a volume at a concentration of 2.0 g/L or greater comprising:
    (a) contacting the protein with a refold buffer comprising a redox component comprising a final thiol-pair ratio having a range of 0.001 to 100 and a redox buffer strength of 2 mM or greater and one or more of:
        (i) a denaturant;
        (ii) an aggregation suppressor; and
        (iii) a protein stabilizer; to form a refold mixture;
    (b) incubating the refold mixture; and
    (c) isolating the protein from the refold mixture.

This appeal arose from a challenge of the '138 patent in an inter partes review by Petitioners Apotex Inc. and Apotex Corp.  In its Final Written Decision, the Board construed the term "final thiol-pair ratio" as meaning "the relationship of the reduced and oxidized redox species used in the redox component of the refold buffer as defined by the [following] equation":
                    [reductant]²
                    [oxidant]

Based on this construction, the Board determined that the Petitioners had demonstrated that claims 1-24 were unpatentable over U.S. Patent Publication No. 2007/0238860 in view of Hevehan and Clark, 54 Biotechnology & Bioengineering 221 (1997).  Amgen appealed the Board's construction and determination of unpatentability, Apotex declined to participate in the appeal, and the USPTO intervened to defend the Board's decision.

On appeal, Amgen argued that the Board misconstrued the term "final thiol-pair ratio" because the claim "language makes clear that the redox component is a distinct volume from the refold buffer, and it is that redox component [rather than the refold buffer] that comprises the claimed 'final thiol-pair ratio'" (emphasis in Appellant's brief).  According to the opinion, the Office "assume[d] that the only way to give meaning to the word 'final' in 'final thiol-pair ratio' and make sense of the '138 patent's claims and specification is to understand 'final thiol-pair ratio' in the context of the ultimate solution—i.e., the refold mixture—rather than specific ingredients therein—e.g., the redox component."

The panel agreed with Amgen, noting that "[a] straightforward reading of the claim language indicates that the 'final thiol-pair ratio' is an attribute of the redox component."  The opinion also notes that the '138 patent specification distinguishes between the terms:

• "final thiol-pair ratio" -- "In various embodiments the redox component has a final thiol-pair ratio" (emphasis in opinion);
• "buffer thiol-pair ratio" – "As used herein, the term 'buffer thiol-pair ratio' is defined by the relationship of the reduced and oxidized redox species used in the refold buffer . . ." (emphasis in opinion); and
• "system thiol-pair ratio" -- "The buffer thiol-pair ratio is, however, only one component in determining the total system thiol-pair ratio in the total reaction" (emphasis in opinion).

In view of the claim language and disclosure in the specification, the panel determined that:

[T]he specification clearly and exclusively describes "final thiol-part ratio" as an attribute of the redox component.  If claim 1 covered a [thiol-pair ratio] calculated in the refold buffer—as the Board construed and analyzed claim 1—claim 1 would have recited a "buffer thiol-pair ratio" rather than "final thiol-pair ratio."

The opinion states that "[t]he Board's construction, which treats the claimed 'final thiol-pair ratio' as an attribute of the redox component in the refold buffer rather than of the redox component independent of the refold buffer, is inconsistent with the plain language of claim 1 and the specification and is therefore unreasonably broad" (emphasis in opinion).  The panel, therefore, held that the Board misconstrued the term "final thiol-pair ratio," and reversed the Board's decision, holding that Apotex had failed to demonstrate that claims 1-24 of the '138 patent were unpatentable under § 103(a).

Amgen Inc. v. Vidal (Fed. Cir. 2022)
Nonprecedential disposition
Panel: Circuit Judges Chen, Schall, and Stoll
Opinion by Circuit Judge Chen