Originally posted on IPKat.
The strict US patentability requirements of written description and enablement do not just apply to antibodies, but may be the downfall of any broadly claimed biologic or biotech platform invention. In Seagen v. Daiichi Sankyo, the court rejected the notion that a broad genus disclosure can support a specific subgenus claim without clear “blaze marks.” The Federal Circuit’s decision is in clear contrast with the European approach of both the EPO and UPC to broadly claimed biotech inventions.
Legal background: Written description and enablement
In the US, the requirements for sufficiency are split into two distinct doctrines of the written description requirement and enablement. The written description requirement necessitates that the patent specification describes the invention in sufficient detail to convey to a skilled person that the inventor had “possession” of the claimed subject matter at the time of filing (35 U.S.C. § 112(a)). This requirement is applied very strictly with respect to antibodies and other biologics, including CAR-T (see Juno v Kite). When applying the test, the US courts often employ an analogy of a forest and trees from In re Ruschig, whereby it is not enough to “plant a forest of generic possibilities”. Instead, one must provide “blaze marks” on the specific trees one wishes to claim.
Enablement is distinct from the written description but is a similarly high-bar. The enablement requirement demands that the specification teaches the skilled person how to make and use the full scope of the claimed invention without undue experimentation. As confirmed by the Supreme Court decision in Amgen v Sanofi, the US approach to enablement for broad functional antibody claims is very strict. According to the reasoning in Amgen v Sanofi, if a claim covers a vast number of functional embodiments, the specification must provide a quality common to every embodiment that allows them to be identified without painstaking trial-and-error. In contrast to the established case law on antibodies in Europe, Amgen v Sanofi was seen as effectively ruling out broad functional antibody claims in the US.
Patentability of antibody-drug-conjugates
The appeal in Seagen v. Daiichi Sankyo concerned the validity of Seagen’s patent US 10808039, covering Daiichi Sankyo and AstraZeneca’s blockbuster ADC, Enhertu. The patent particularly related to antibody-drug conjugates (ADCs) for treating cancer. ADCs comprise an antibody that targets a specific antigen on a cancer cell, a toxic drug moiety, and a linker that connects the two. ADCs often use a repurposed antibody in combination with a known cytotoxic drug. This presents obvious patentability challenges for the new ADC product absent something novel and inventive relating to the structure of the ADC, such as the linker between the antibody and cytotoxic drug.
In the present case, the invention concerned the composition of the peptide linker connecting the antibody and the cytotoxic drug. Claim 1 defined an ADC where the linker comprised a chain of four amino acids consisting only of glycine (Gly) and phenylalanine (Phe) residues.
The Defendants in the case, Daiichi Sankyo and AstraZeneca, market a highly successful ADC product, Enhertu (trastuzumab deruxtecan). Enhertu uses a linker falling under the definition of the patent (Gly-Gly-Phe-Gly). On appeal, the key question for the Federal Circuit was whether the priority application provided adequate written description support for the claimed linker. If the priority application failed to support the claims, the patent would lose its priority date, and the later disclosure of Enhertu would anticipate and invalidate the patent in question.
Written description in the priority application: The “blaze mark” theory
The Patentee argued that the priority application provided sufficient support for the granted claim. They pointed out that the priority application disclosed that the linker could be a tetrapeptide and listed glycine and phenylalanine as possible amino acids. The Defendants argued in response that the priority application merely disclosed a vast genus of potential peptides without pointing to the specific claimed subgenus. The priority application, instead of disclosing a four amino acid chain consisting only of Gly and Phe residues, merely provided a generic disclosure of peptide units that could range from dipeptides to dodecapeptides and listed 83 possible amino acid options for each position.
On appeal, the Federal Circuit agreed with the Defendants. The Federal Circuit noted that for tetrapeptides alone, the number of possible combinations based on the disclosure in the priority application “exceeded 47 million”, whilst the subsequently claimed Gly/Phe-only subgenus consisted of 81 specific sequences. The Federal Circuit concluded that the disclosure of such a “broad genus” in the priority application was inadequate to satisfy the written description requirement for the particular subgenus claimed (page 11): “although the 81 claimed Gly/Phe-tetrapeptides are ‘encompassed’ within those 47 million […] they are merely an infinitesimal fraction of those peptide units generally included” (page 11). Applying the Ruschig analogy, the court found that the priority application merely presented a forest of unmarked trees.
In support of their patent, the Patentee attempted to rely on a “blaze mark” theory, arguing that a skilled artisan would be directed to the claimed subgenus by starting with a specific example in the text (GFLG) and modifying it based on other disclosures. The Patentee’s expert testified that it would be a “straightforward leap” to go from the disclosed examples to the claimed invention. The Federal Circuit was not convinced, instead finding that the expert testimony was self-defeating and doomed the Patentee’s case. For the Federal Circuit, “that which one must leap to is obviously not there” (page 15).
The Federal Circuit thus concluded that the patent was invalid for lack of written description, as the priority document failed to direct the skilled person to the specific subgenus of linkers used in the competitors’ product.
Enablement of a functional definition
The Federal Circuit also addressed the issue of enablement. The granted claim at issue particularly did not specify the structure of either the antibody or the cytotoxic drug. The claim merely specified that the cytotoxic drug was “intracellularly cleaved” from the antibody in the patient. The claim was therefore construed as covering an ADC containing any drug moiety with the recited function. The Defendants argued that the claims were thus not enabled because this functional definition encompassed a vast and unpredictable range of candidates.
The Federal Circuit agreed with the Defendants, citing the Supreme Court’s decision in Amgen v Sanofi. The court noted that the specification failed to disclose “a quality common to every functional embodiment”. Given the unpredictability of ADCs, the Federal Circuit concluded that a skilled person would be forced to perform “trial-and-error discovery” to determine which of the potentially millions of drug moieties would function as claimed. The Federal Circuit therefore found that the claims were also invalid for lack of enablement. The decision of the district court was reversed, and the patent was found invalid.
What about infringement?
The issue of infringement itself was not at issue on appeal. The jury at the District Court had previously found that Daiichi’s Enhertu wilfully infringed the patent and had awarded Seagen damages. The financial consequences of the District Court decision were significant, with the jury awarding an upfront payment of nearly $42 million plus an 8% running royalty on future sales. However, Daiichi chose not to challenge this specific finding before the Federal Circuit, and instead focussed on challenging the validity of the patent. Given that an invalid patent cannot be infringed, the jury finding in the District Court of wilful infringement, and the significant damages award, was vacated in view of the Federal Circuit’s finding that the patent was invalid.
US versus European approach to biotech platforms
This case is yet further confirmation that the strict written description and enablement requirements are not just a challenge for antibodies, but apply also to other biologics, including ADCs and cell therapies, and is particularly applicable to platform inventions.
At its heart, the fundamental difference between the US and Europe on platform and broad functional claims lies in what is considered “undue trial and error” for the skilled person. Following Amgen v Sanofi, the US considers the very scale of a task of performing all the millions of embodiments within a functional definition to undermine the patentability of the claim. As the US Supreme Court reasoned, “the more a party claims, the broader the monopoly it demands, the more it must enable”.
The EPO, by contrast, does not consider the amount of experiments that a skilled person needs to do as relevant to whether the skilled person can perform the invention over the whole scope of the claim. In Europe, routine experimentation is not limited or determined by the time or cost of the experiments. Instead, what matters in Europe is whether a skilled person would be equipped with the skills and resources to carry out the invention without employing inventive skill. This means that broad functional claims fall down in Europe not because of the number of potential embodiments that must be screened, but because a skilled person would not be able to perform the screen without a further inventive step (see T 0435/20). The UPC Court of Appeal has recently confirmed its alignment with the EPO approach.
Despite the divergence in US and European case law on biologics, the present case is nonetheless reminiscent of a few decisions from the EPO this year, most notably the Board of Appeal case finding that the sufficiency of an invention must be satisfied at the priority date (T 0883/23). Like the Board of Appeal case, Seagen v. Daiichi Sankyo is a warning that the patentability requirements for an invention must be satisfied at the priority date. To be confident of a valid priority claim, one cannot merely file a placeholder and hope to define or sufficiently support the invention with data later on. Interestingly, the decision in the present case on written description also brings to mind the EPO added matter test, whereby a reach-through selection for a subspecies from a broad genus is not permissible without a pointer towards the selection.
Analysis
The present case is confirmation of the significant challenges associated with protecting biotech platform inventions under the current US patent system. By their very nature, platform inventions will cover a vast array of embodiments. The strict approach of the US courts to both enablement and written description raises the question of whether a patentee can ever provide enough information to support a broad platform invention. It has been suggested that in silico data may help to bridge this gap. However, for this Kat, the increased availability of in silico data could on the contrary make the situation worse, by making it easier for challengers to find unworkable embodiments falling within the scope of a broad claim. More thoughts on this to follow.
Author: Rose Hughes
Rose is a biotech and pharmaceutical patent specialist with over a decade of experience in intellectual property. Rose is a patent attorney at Evolve, where she leverages our unique fractional in-house model to provide clients with deep patent law expertise combined with the strategic commercial oversight typically associated with senior in-house counsel.
With a PhD in Immunology from UCL, Rose applies her technical background to complex innovations in biologics, cell and gene therapies, and the rapidly emerging field of AI-assisted drug development. Previously, Rose held the role of Director. Patents at AstraZeneca, where she was responsible for global IP portfolios and IP strategy at every stage of the pharmaceutical pipeline, from platform development and on-market commercialization to SPCs and patent term extensions.
A recognized thought leader in the field, Rose has been a regular contributor to IPKat since 2018, offering practical insights into European patent law developments. She is also a frequent speaker on the epi podcast, a guest lecturer for the Brunel University IP law Postgrad Certificate, and a contributing author to published books A User’s Guide to Intellectual Property in Life Sciences (2021) and Developments and Directions in Intellectual Property Law (2023).
