Factual and Procedural Background
This opinion concerns a patent dispute between Company A and Company B relating to patents covering lyophilised formulations of monoclonal antibodies, specifically trastuzumab, the active ingredient in a breast cancer drug targeting the HER2 receptor. The patents in issue are EP (UK) 1 516 628 and EP (UK) 2 275 119, both divisionals filed in 1996 claiming priority from 14 March 1996. The patents relate to stable isotonic lyophilised protein formulations comprising trastuzumab and certain excipients (polysorbate 20, histidine, and trehalose).
Company A seeks to sell a generic version of trastuzumab now that the supplementary protection certificate protecting the original drug has expired. Company A challenges the validity and allowability of proposed amendments to the patents by Company B, which no longer defends the granted claims but relies on amended claims. Company A contends the amended claims are invalid for obviousness, insufficiency, and impermissible amendment (extension of scope, added matter, and clarity).
The court heard expert evidence from formulation scientists and clinicians called by both parties and considered the common general knowledge of the skilled person, comprising a team including a formulation scientist and a clinical oncologist.
Legal Issues Presented
- Are the proposed amended claims allowable as amendments under the Patents Act 1977 and EPC, specifically regarding extension of scope, added matter, and clarity?
- Are the proposed amended claims valid, in particular, do they involve an inventive step or are they obvious over the prior art and common general knowledge?
- Are the claims sufficiently disclosed and supported by the original patent application?
- How should product by process claims, particularly claims "obtainable by" lyophilisation, be construed and treated for validity and allowability?
Arguments of the Parties
Company A's Arguments
- The amended claims extend the scope of protection impermissibly by deleting certain limitations and by covering formulations with multiple antibodies or lyoprotectants not originally claimed.
- Claims contain added matter due to intermediate generalisation from a narrow example in the specification to broader claim language, particularly regarding protein concentration and lyophilisation conditions.
- The product by process language ("obtainable by lyophilising") fails clarity requirements because it does not specify which product characteristics are defined by the process, rendering the claim indefinite.
- The claims lack inventive step as the skilled person would have been motivated to formulate trastuzumab using routine screening of common excipients, including trehalose, histidine, and polysorbate 20, based on prior art such as Carter and common general knowledge.
- Concerns about toxicity or regulatory hurdles for trehalose would not have deterred the skilled formulator from testing it.
- The claims are insufficient as the patent does not clearly disclose stable formulations across all claimed concentrations.
Company B's Arguments
- The proposed amendments do not extend the scope because the molar ratio limitation is effectively maintained by the "obtainable by" lyophilisation clause, and the fallback amendment replacing "comprising" with "consisting of" further limits scope.
- The product by process claims are necessary as there is no alternative way to define the claimed product's characteristic other than by referring to the process used to make it.
- The amended claims are clear and supported by the application as filed, relying on established case law allowing certain broadenings of claim language.
- Trehalose was not excluded from common general knowledge as a lyoprotectant, and concerns about toxicity and regulatory approval were known but would not render its use inventive.
- The skilled person would not be deterred from including trehalose in screening despite the existence of other excipients and the empirical nature of formulation work.
- The claims are valid and inventive, as the prior art and common general knowledge do not teach the specific stable lyophilised formulations claimed.
Table of Precedents Cited
| Precedent |
Rule or Principle Cited For |
Application by the Court |
| KCI Licensing v Smith & Nephew [2010] EWHC 1487 |
Definition and understanding of common general knowledge in patent cases. |
The court relied on Arnold J's summary of the law on common general knowledge, approved by the Court of Appeal. |
| Kirin-Amgen [2005] RPC 9 |
General principles of claim construction, including product by process claims. |
Guided the court's approach to claim interpretation and the treatment of product by process claims. |
| Regeneron v Genentech [2013] EWCA Civ 93 |
Treatment of functional technical features in claims, particularly for therapeutic indications. |
The court accepted that treatment of HER2 positive breast cancer is a functional technical feature of the claims. |
| General Tire [1972] RPC 457 |
Concept of "good basis for further action" in assessing common general knowledge. |
The court rejected the argument that toxicity concerns excluded trehalose from common general knowledge as a good basis for further action. |
| Bonzel v Intervention [1991] RPC 553 |
Approach to added matter in patent amendments. |
Used as foundational authority for added matter analysis. |
| Vector v Glatt [2007] EWCA Civ 805 |
Intermediate generalisation and added matter principles. |
Applied to assess whether amendments introduced impermissible intermediate generalisations. |
| AC Edwards v Acme [1992] RPC 131 |
Permissibility of amendments broadening claim language without adding new matter. |
Company B relied on this line of authority to support amendments broadening claim scope. |
| Texas Iron Works [2007] RPC 207 |
Support for AC Edwards principle on added matter. |
Supported Company B's position on allowability of broader claim language. |
| AP Racing v Alcon [2014] EWCA Civ 40 |
Added matter and claim language interpretation. |
Considered by the court in relation to added matter arguments. |
| Pozzoli v BDMO [2007] EWCA Civ 588 |
Structured approach to assessing inventive step (obviousness). |
The court applied the Pozzoli framework to evaluate inventive step. |
| Conor v Angiotech [2008] UKHL 49 |
Assessment of obviousness; weighing relevant factors. |
The court applied the principles set out by Lord Hoffmann on obviousness. |
| Medimmune v Novartis [2012] EWCA Civ 1234 |
Clarification that obviousness is a single question of fact. |
The court followed the approach emphasizing the holistic factual inquiry into obviousness. |
| Kirin-Amgen [2002] EWCA Civ 1096; [2003] RPC 3 |
Novelty and product by process claims; process does not confer novelty unless it imparts a new characteristic. |
The court aligned UK law with EPO practice on product by process claims and novelty. |
| Zipher v Markem [2008] EWHC 1379 |
Discretionary factors in amendment allowability under s75(5) Patents Act. |
Referenced regarding the court's approach to amendments post-Kirin-Amgen. |
| Molynlycke v Brightwake [2011] EWHC 376 |
Warning against hindsight in assessing obviousness. |
The court considered the caution against hindsight in evaluating inventive step. |
Court's Reasoning and Analysis
The court began by identifying the skilled person as a multidisciplinary team including a formulation scientist and a clinical oncologist. It carefully examined the common general knowledge as of the priority date, finding that while the existence of trastuzumab and the phase III trial was publicly known to some, it was not part of the common general knowledge of the skilled person. The court found that the excipients histidine, polysorbate 20, and trehalose were part of the common general knowledge as potential formulation components, with trehalose known as a lyoprotectant but not previously used in parenteral therapeutic formulations due to regulatory and toxicity considerations.
The court analyzed the proposed claim amendments, focusing on extension of scope, product by process claim construction, clarity, and added matter. It concluded that the amendments as proposed would extend the scope impermissibly because the claims could cover formulations with multiple antibodies or lyoprotectants not covered by the granted claims. The fallback amendment replacing "comprising" with "consisting of" cured this defect.
Regarding product by process claims, the court adopted the established EPO approach that a product "obtained by" a process claim is limited to products actually made by that process, while novelty requires a new characteristic conferred by the process. The claim language "obtainable by" lyophilising the Table 5 Solution lacked clarity because it did not specify the characteristic defined by the process, leading to an indefinite claim. The court rejected the amendment allowing such claims without clear definition of characteristics.
On added matter, the court found that the amendments introduced new information by generalizing from the narrow example in the patent to broader claim language, particularly by omitting any limitation on protein concentration, which was a parameter affecting stability. The claims thus added matter beyond the original disclosure.
In the obviousness analysis, the court applied the Pozzoli framework and relevant authorities, considering the prior art Carter papers and common general knowledge. It found that the skilled team would be motivated to formulate trastuzumab and would conduct routine screening of excipients including histidine, polysorbate 20, and trehalose. Concerns about trehalose toxicity and regulatory approval would not deter testing. The claimed formulations were thus obvious. The court rejected arguments that the claimed invention was an arbitrary selection or required an inventive research program, noting the empirical nature of formulation work and the routine nature of the screening approach.
The court found no need to consider insufficiency or inventive step over the other prior art (Draber) given its findings.
Holding and Implications
The court's final decision is as follows:
EP (UK) 2 275 119 is revoked.
EP (UK) 1 516 628 is to be amended by deleting claims 1 to 6, leaving claims 7 to 11 (which will be renumbered).
The direct effect is that Company A succeeds in its challenge and Company B's proposed amendments are not allowed as filed. The court found all the amended claims invalid for lack of inventive step and added matter. The decision does not establish new precedent beyond applying established principles regarding product by process claims, added matter, and obviousness in the context of pharmaceutical formulation patents.