How to mitigate prior art traps for follow-on pharma patents

Changes to the European Medicines Agency’s approach to publishing clinical trial data are exacerbating the prior art traps that already affect pharmaceutical innovators – traps that pose significant commercial risks, especially given the growing importance of follow-on patents for drugmakers’ commercial strategies. However, there are several steps that branded pharma companies can follow to mitigate these dangers.

Initial patents for new pharmaceutical products typically claim the product itself (‘composition of matter’ or COM patents). As COM patents approach expiry, follow-on patents can be obtained to protect improvements made to the original product (such as new analogues and formulations) or to protect new clinical findings (such as new therapeutic indications or dosage regimens). Such follow-on patents allow companies to maximise value from their original investment.

Patent filing data from the EPO suggests that follow-on patents are commercially significant and, in some respects, becoming more important.

As Figure 1 shows, overall activity in the A61 CPC classification (Medical or Veterinary Science; Hygiene) has increased substantially over time.

A similar trend exists for A61P classifications, used for inventions directed to particular medical indications, including second medical use claims. A61P filings largely track the trajectory of total A61 filings, moving in line with the wider category. This is consistent with the central role of therapeutic activity claims within pharmaceutical patenting.

By contrast, the formulation (A61K9/00) and excipient / carrier (A61K47/00)classifications display a more consistent upward trajectory. While overall A61filings experience periods of stagnation or decline, these categories exhibit steadier, continuous growth.

Given the growing significance of follow-on patents, however, it is important to note the distinctive prior art risks that affect these IP rights.

As a product progresses through its lifecycle, an increasing amount of information becomes publicly available as prior art against follow-on patent applications. For example, companies must submit clinical trial applications to national authorities and this material is then published, which can disclose information such as dosages, formulations, administration routes or dosage regimens.

The potential impact of such publications is demonstrated by the history of eculizumab. In 2008, Alexion filed a follow-on patent application directed to the use of eculizumab in a new clinical indication, the neuromuscular disease myastheniagravis. However, the prior publication of the corresponding phase 2 clinical trial was held by the EPO’s Board of Appeal to render the claimed use obvious and the follow-on patent application was refused.

The EU will publish clinical trial information earlier

These dangers are being increased by the fact that new guidance by the European Medicines Agency means that trial information will now be published earlier than before. Patent strategies must adapt to this framework.

Previously, sponsors could defer for up to seven years the publication of documents that contain commercially confidential information (CCI), such as a clinical trial protocol describing study rationale, patient subgroups, the product and the dosing regimen. Sponsors could then file patent applications during the deferral period without having such information available as prior art.

This deferral system has now been removed. Documents will be published according to a predefined timetable, depending on the specific type and phase of the clinical trial, but sponsors may redact CCI.

However, the onus will be on sponsors to ensure that redaction is accurate. As an example, protocols for phase 2 and phase 3 clinical trials will be published up on the decision to allow the trial. Such early disclosures must now be borne in mind when planning follow-on patent applications.

Furthermore, sponsors must now also enter standardised information termed structured data for clinical trial applications. Structured data will document information such as trial characteristics (for example, the phase and therapeutic area), patient groups (for example, adult or paediatric) and trial logistics (such as start and end dates). Structured data is published when a decision is made to allow the trial, but structured data cannot be redacted. Thus, structured data can also produce prior art against follow-on patent applications.

The data in Figure 2 reinforces why this matters commercially. A61P (relating to specific medical indications) alone accounts for a significant share of all A61 filings,notwithstanding the breadth of subject matter captured within A61 more generally.However, the share represented by A61K9/00 (relating to formulations) andA61K47/00 (covering excipients and carriers) has increased gradually over time,indicating that such filings are becoming more prominent within the overall pharmaceutical patent landscape. Those are precisely the kinds of follow-on inventions for which clinical trial disclosures can be sensitive.

Strategic impact

The result of all this is that follow-on claims may be narrower and more vulnerable to invalidity challenges. This can compress the effective exclusivity period, bringing the point of meaningful competition closer to the end of the original COM term.

Even small reductions in that exclusivity tail can have a major commercial impact through earlier generic or biosimilar entry and reduced pricing flexibility.

This dynamic feeds directly into valuation. While follow-on patents can provide extensions to exclusivity, their scope and durability are inherently less predictable than COM patents, which continue to dominate loss-of-exclusivity projections.

In Europe, where patentability thresholds for certain follow-on claims have become more demanding, this relative uncertainty may persist. As a result, the timing of filings relative to public disclosures is increasingly viewed as an indicator of risk, and investors are placing greater emphasis not only on the presence of follow-on filings, but on the existence of a well-coordinated and credible strategy that integrates R&D, regulatory and IP considerations.

The filing trends discussed above help explain that investor focus. If formulation and excipient/carrier filings are taking a larger share of pharma patenting activity over time, then more value may depend on categories of patents that can be vulnerable to disclosure-based attacks. That has obvious implications for internal portfolio valuation as well as external diligence.

These factors are also gaining traction in transactions. In licensing, M&A and financing, due diligence is starting to focus on the relationship between disclosure timelines and patent filing strategies. A common exercise is to map disclosure history against priority and filing dates to assess whether follow-on claims, particularly those dependent on clinical data such as dosage regimens and formulations, may be vulnerable to novelty or inventive-step attacks.

Strategies to adapt to the new EMA guidance

This leaves patent applicants with a high-stakes dilemma.

Submitting applications before clinical trial information enters the public domain reduces the risk of detrimental disclosures, but such early filings may not contain enough efficacy data to fully support patentability. Conversely, filing after trial information becomes publicly available may mean that stronger clinical data can be included, but such applications will face a higher prior-art burden.

Taking the sting out of this dilemma requires regulatory departments to understand what will be published and when, and to coordinate with IP departments to en sure that the timing of follow-on applications is planned.

A first means to mitigate against premature disclosure is to ensure that an accurate redaction process is in place for clinical trial data that is to be published. Research,intellectual property and regulatory departments should be in close contact when filing clinical trial applications so as to redact CCI and disclose only the minimum material necessary for the application.

A second means is to file your follow-on patents before clinical trial information is published but to include extensive preclinical data in those applications. For example, in vitro experiments can demonstrate improved drug formulations and animal models can establish credibility of medical use claims for new therapeutic indications. It may also be possible to pursue a staged filing strategy where an any newly obtained clinical data.Applicants may also attempt to rely on post-filing data to demonstrate claimed technical effects.

A third means is to utilise a broad initial filing such that divisional applications can be pursued thereafter. For example, a specification for a follow-on application to a new clinical indication may be drafted such that there is basis for claims directed to the new indication itself, particular patient subgroups, dosing regimens and/or formulations. Redaction in the published trial information can be tailored such that,even if a published clinical trial prevents patenting of, for example, a new clinical indication, claims may still be pursued for other subject matter.

Authors:
‍Stuart McKellar - Patent Scientist
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George James - Senior Associate, UK and European Patent Attorney