## Facts

- Roche Diagnostics GmbH (then known as Boehringer Mannheim GmbH) owned European Patent (UK) No. 0 607 156 covering preserved, multi-dose injectable liquid formulations (“parenterals”) with protein active ingredients.
- As granted, the patent claimed parenteral formulations preserved with one or more of three known antimicrobial preservatives—chlorobutanol, benzyl alcohol, and benzalkonium chloride—used alone or in combination up to stated concentrations (up to about 2%).
- Sandoz GmbH brought an action in the High Court (Chancery Division, Patents Court) seeking revocation on the ground that the patent lacked an inventive step.
- In response, Roche applied to amend the patent before and at trial to narrow the case to:
  - parenterals containing erythropoietin (EPO); and
  - the use of a combination of at least two of the three specified preservatives (rather than any one preservative alone), generally at lower levels.
- By agreement, questions about whether the court should allow the amendment as a matter of discretion were postponed; the hearing and judgment addressed only whether the patent would be valid on the basis of the proposed amended claims.
- The priority date was 15 August 1991. The skilled addressee was a team working on formulation of injectable protein products, with knowledge of preservative efficacy, product stability, and practical constraints for multi-dose parenterals.
- It was common ground that multi-dose parenterals normally require antimicrobial preservation, and that formulation choices must balance microbial control against risks such as protein instability and patient tolerability.
- Sandoz argued that, by 1991, it was standard practice to screen known preservatives and combinations at reduced individual concentrations to meet antimicrobial requirements while limiting adverse effects, and that the amended claims described no more than that routine work.
- Roche argued that the skilled team would not have treated chlorobutanol and benzalkonium chloride as realistic options for an EPO product because of concerns about compatibility with proteins and other practical or regulatory considerations.
- Sandoz relied on (i) common general knowledge and (ii) two main strands of prior art: WO 91/11200 (“Konings”), and microbiology literature including a 1985 review by Denyer and related papers discussing combined preservative use and improved antimicrobial performance when agents are used together.

## Issues

1. Whether, as of 15 August 1991, the amended claims (EPO parenterals preserved by a combination of at least two of chlorobutanol, benzyl alcohol, and benzalkonium chloride at low levels) involved an inventive step under section 3 of the Patents Act 1977.
2. Whether, given common general knowledge, the amended claims were an obvious “try and test” selection and optimisation exercise using known preservatives and known combination strategies for multi-dose injectables.
3. What, if anything, WO 91/11200 (Konings) and the Denyer literature would lead the skilled team to do when formulating a preserved multi-dose EPO product at the priority date.
4. Whether the asserted concerns about chlorobutanol and benzalkonium chloride meant the skilled team would have excluded them from consideration for EPO parenterals, rather than treating them as candidates to be tested at lower levels and in mixtures.

## Decision

- The court (Patten J) held that the patent, if amended as proposed, would be invalid for lack of inventive step.
- The claimed approach—selecting from well-known preservatives and using them in combination at reduced individual concentrations to achieve adequate antimicrobial effect while checking protein stability—was treated as a standard formulation route the skilled team would pursue.
- The court rejected Roche’s case that the claimed combination strategy for EPO reflected an inventive departure from what the skilled team would do at the priority date.
- Sandoz therefore succeeded on the validity challenge addressed in this judgment, subject to the separate, deferred question of whether the amendment should be permitted as a matter of discretion.

## Legal Principles

- Inventive step under the Patents Act 1977 is assessed at the priority date by reference to what the skilled person (or skilled team), equipped with common general knowledge and the state of the art, would have found obvious.
- In formulation cases, a claim can be obvious where it amounts to selecting from a known range of options and carrying out routine experiments and optimisation to reach workable concentrations and mixtures.
- The need to run experiments does not itself establish inventiveness when the experiments are part of a straightforward program the skilled team would adopt to solve a known formulation problem.
- Prior art that teaches the general utility of using more than one preservative, and the known practice of reducing individual amounts when agents are used together, can make a claimed combination strategy obvious even if the art does not name the exact product being formulated.
- A party resisting obviousness cannot succeed merely by pointing to general caution about certain excipients if, on the evidence, those excipients would still have been treated as candidates that a formulator would consider and test, particularly at lower levels or in mixtures.

## Conclusion

The High Court held that Roche’s proposed amended claims—limited to multi-dose EPO parenterals using combinations of at least two of three known preservatives at low concentrations—would have been obvious to the skilled formulation team at the 1991 priority date in light of common general knowledge and the cited prior art, so the amended patent lacked an inventive step and was invalid (with amendment discretion left for later).


Sandoz GmbH v. Roche Diagnostics GmbH, [2004] EWHC 1313 (Ch), HC-2003-03648 (2004)