Introduction

The case of Sandoz AG & Ors v Bayer Intellectual Property GmbH & Ors ([2024] EWCA Civ 562) represents a pivotal moment in pharmaceutical patent law, particularly concerning the concept of obviousness in the development of dosing regimens. This litigation centered around the validity of European Patent (UK) No. 1 845 961, which protected the use of rivaroxaban—a leading anticoagulant marketed by Bayer under the trademark Xarelto—for once-daily administration in treating thromboembolic disorders.

The parties involved included Bayer, the patent holder and alleged exclusive licensee, and various generic pharmaceutical companies aiming to market rivaroxaban following the expiry of a supplementary protection certificate on 1 April 2024. The Respondents sought revocation of the patent to allow for the production of once-daily generic rivaroxaban, whereas Bayer counterclaimed based on potential patent infringement.

Summary of the Judgment

The High Court Judge, His Honour Judge Hacon, initially revoked Bayer's patent, a decision which Bayer appealed to the England and Wales Court of Appeal (Civil Division). Upon review, the Court of Appeal dismissed Bayer's appeal, affirming the High Court's decision. The core issue pertained to whether the inclusion of a once-daily dosing regimen in a Phase II clinical trial for rivaroxaban was obvious, thereby lacking an inventive step as required for patent validity.

The Court concluded that, based on the existing Phase I data presented in prior art documents ("Harder" and the "Kubitza posters"), it was obvious for a skilled team to include a once-daily dosing regimen in Phase II trials with a reasonable expectation of success in terms of both efficacy and safety. Consequently, the patent claim was deemed obvious and thus invalid.

Analysis

Precedents Cited

The judgment extensively referenced foundational cases in patent law to underline the standards for obviousness. Key among these were:

• Generics (UK) Ltd v H. Lundbeck A/S [2007] EWHC 1040 (Pat)
• Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] UKHL 49
• Actavis Group PTC EHF v ICOS Corporation [2019] UKSC 15
• Novartis AG v Generics (UK) Ltd [2012] EWCA Civ 1623
• Volpi v Volpi [2022] EWCA Civ 464

These cases collectively establish that for an invention to lack an inventive step (and hence be obvious), it must be demonstrable that the skilled person would have found the invention evident based on prior art and common general knowledge. The Court of Appeal adhered to these precedents, emphasizing a case-by-case analysis where all relevant factors are weighed.

Legal Reasoning

The Court's legal reasoning hinged on whether the inclusion of a once-daily dosing regimen in Phase II trials was an obvious step for a skilled team, considering the prior Phase I data. The judge analyzed the following key points:

• Common General Knowledge: The process and considerations involved in designing clinical trials, particularly Phase II, were considered established knowledge.
• Prior Art Evaluation: The prior Phase I studies ("Harder" and the "Kubitza posters") provided sufficient data suggesting the feasibility and safety of once-daily dosing.
• Reasonable Expectation of Success: Based on the pharmacokinetic (PK) and pharmacodynamic (PD) data, there was a reasonable basis to expect that once-daily dosing could be both safe and effective.
• Ethical Considerations: While ethical review committees oversee trial safety, the decision to include once-daily dosing was deemed a technical consideration rather than a mere ethical one.

The Court concluded that there was no inventive step in claiming the once-daily regimen, as it was an obvious extension of existing data and common practices in clinical trial design.

Impact

This judgment has profound implications for pharmaceutical patents:

• Patent Drafting: Innovators must ensure that their patent claims encompass non-obvious inventive steps, especially when extending existing treatments or dosing regimens.
• Generic Drug Market: The clarification on obviousness criteria expedite the entry of generic drugs, promoting competition and potentially reducing healthcare costs.
• Clinical Trial Design: While pharmaceutical companies continue to design diverse dosing regimens in trials, they must be aware that merely varying dosing frequency without a clear inventive step may not be patentable.

Moreover, the decision underscores the judiciary's commitment to balancing patent protection with the public interest in accessible medicines.

Complex Concepts Simplified

Obviousness

In patent law, a claim is "obvious" if someone skilled in the relevant field would find it evident based on existing knowledge and prior art. If a patented invention lacks originality beyond what was already known or predictable, it fails the inventive step requirement.

Phase I and Phase II Clinical Trials

Phase I: Initial testing in a small group of healthy volunteers to assess safety, dosage, and pharmacokinetics (how the drug moves through the body).
Phase II: Expanded trials involving patients with the target condition to evaluate efficacy and further assess safety. Different dosing regimens are often explored to determine optimal treatment protocols.

Pharmacokinetics (PK) and Pharmacodynamics (PD)

Pharmacokinetics (PK): Studies how the body absorbs, distributes, metabolizes, and excretes a drug. Key parameters include the drug's half-life, which influences dosing frequency.
Pharmacodynamics (PD): Examines the biological effects of the drug on the body, including mechanisms of action and the relationship between drug concentration and effect.

Conclusion

The Court of Appeal's decision in Sandoz AG & Ors v Bayer Intellectual Property GmbH & Ors solidifies the application of the obviousness standard in pharmaceutical patent law. By determining that the inclusion of a once-daily dosing regimen for rivaroxaban in Phase II trials was an obvious step based on existing Phase I data and common general knowledge, the judgment emphasizes the necessity for genuine inventive steps in patent claims.

This ruling promotes a balanced approach, ensuring that patents do not stifle competition and innovation while still encouraging genuine advancements in medical treatments. Pharmaceutical companies are thus encouraged to pursue truly novel and non-obvious innovations to secure robust patent protections, ultimately benefiting the broader public with access to effective and affordable medications.