Incorporated References Sufficient to Establish Anticipation
Incorporated References Sufficient to Establish Anticipation

In Arbutus Biopharma Corporation, FKA Protiva Biotherapeutics, Inc. V. Modernatx, Inc., FKA Moderna Therapeutics, Inc. (Fed. Cir. 2020-1183, April 11, 2023), Moderna challenged claims 1–22 of Arbutus’ U.S. Patent No. 9,404,127 (the ’127 Patent) by Inter Partes Review. The Board found all challenged claims anticipated by U.S. Patent 8,058,069 (Yaworski). The Board’s determination of anticipation relied on inherency and the disclosure of documents incorporated by reference by both Yaworski and the ’127 Patent.

The ’127 Patent was directed to compositions of stable nucleic acid-lipid particles (SNALP). Nucleic acids may be useful therapeutic agents. One particular application discussed in the ’127 Patent is delivery of ribonucleic acids (RNA) that participate in the phenomenon of RNA interference. This can be used as a research tool to shut down gene expression, and potentially as a therapeutic. Another application may be gene therapy – delivering a functional gene where the patient suffers because of a missing or dysfunctional gene. Nucleic acids may also encode antigens and, thus, may be useful as a nucleic acid-based vaccine. Indeed, the COVID-19 vaccines most widely distributed are mRNA vaccines where the mRNA encodes a SARS-CoV-2 Spike protein. However, nucleic acids delivered directly to a patient would rapidly degrade and would not reach the intended target tissue. SNALP technology attempts to overcome this delivery problem by surrounding the nucleic acid with a protective coat of lipids.

The ’127 Patent claim 1 is representative and recites:

A composition comprising:
a plurality of nucleic acid-lipid particles, wherein each particle in the plurality of particles comprises:
(a) a nucleic acid;
(b) a cationic lipid;
(c) a non-cationic lipid; and
(d) a conjugated lipid that inhibits aggregation of particles,
wherein at least about 95% of the particles in the plurality of particles have a non-lamellar morphology.

The final clause of claim 1, the “Morphology Limitation,” was at issue. A “lamellar morphology” is where the lipids form in bilayers that are then layered on one another. The nucleic acids are situated between the layers. An example of a non-lamellar morphology is an inverse hexagonal structure where the lipids coat nucleic acid and the coated nucleic acids gather in a hexagonal shape when viewed in cross-section.

The ’127 Patent was based on a “surprising discovery” that the Morphology Limitation can be met by controlling the lipid composition, and the formation process. According to the ’127 Patent there are two formation processes: (1) a Stepwise Dilution Method (SDM) and (2) a Direct Dilution Method (DDM). The details of how to carry out SDM and DDM were incorporated by reference to U.S. pre-grant publication Nos. 2004/0142025 and 2007/0042031 (the ’031 Pub.), respectively.

Yaworski includes common inventors to the ’127 Patent and is commonly owned by Arbutus. The common source of both the ’127 Patent and Yaworski explains the pivotal pieces of the case: They both describe compositions “with almost identical wording,” and they both incorporate the ’031 Pub. by reference. Yaworski also incorporated several other references, but did not explicitly disclose the Morphology Limitation. The Board, however, found that the Morphology Limitation was inherently anticipated by Yaworski “and its disclosures” because it is “an inherent property or natural result of the disclosures.”

The Federal Circuit emphasized the doctrine of inherency: “A limitation is inherent if it is the ‘natural result flowing from’ the prior art’s explicit disclosure.” Schering Corp. v. Geneva Pharms., 339 F.3d 1373, 1379 (Fed. Cir. 2003). “A patent ‘can be invalid based on inherency when the patent itself makes clear that a limitation is ‘not an additional requirement imposed by the claims . . . but rather a property necessarily present’.” Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1332 (Fed. Cir. 2020) (quoting In re Kubin, 561 F.3d 1351, 1357 (Fed. Cir. 2009)) Also, “[i]nsufficient prior understanding of the inherent properties of a known composition does not defeat a finding of anticipation.” Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1349 (Fed. Cir. 1999). Then the Federal Circuit turned to the effect of incorporated references: “When a reference or material from various documents is incorporated, they are ‘effectively part of the host document as if [they] were explicitly contained therein.” Advanced Display Sys., Inc., 212 F.3d at 1282.

Moderna argued that the Morphology Limitation was the “natural result” and an “inherent property” of Yaworski because (1) Yaworski used the same formulation and (2) by following the DDM method as disclosed by Yaworski and its incorporated references, one skilled in the art would necessarily produce the Morphology Limitation. Arbutus countered that DDM, as known in the art, is not a specific method but a genus of methods – some of which would not yield the Morphology Limitation.

The Federal Circuit explained that Yaworski did not disclose a genus of DDM processes, but instead disclosed the exact process to arrive at the Morphology Limitation: “[the] processes and the apparatuses for carrying out these direct dilution processes are described in detail in [the ’031 publication].” Accordingly, the Court held that there was no error in the Board’s conclusion that Yaworski and its incorporated disclosures disclosed the “same formulations and the same DDM as the ’127 Patent.” Further, the combination of the same formulations and the same DDM “would naturally result in a composition having the claimed morphology property.” The Federal Circuit affirmed the Board’s finding that claims 1, 3, and 8–12 are anticipated and invalid.

A patent that incorporates another document by reference includes the disclosure of the incorporated document as if it was explicitly contained in the patent. Patent practitioners have long relied on incorporation by reference in connection with United States patents to establish sufficient support for a claimed invention under 35 U.S.C. § 112. Here, however, the incorporated material did not rescue claims of the patent in which the material was incorporated. Instead, the incorporated material was used to establish anticipation of claims of the ’127 Patent, ultimately rendering the claims invalid. Patent challengers should look not only to the four corners of a prior art patent or patent publication when assessing patent validity, but also to the disclosure in each of the documents incorporated by reference in the patent or patent publication as additional potential resources.

Tags: Biotech



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