Smithkline Beecham Plc & Ors. v Apotex Europe Ltd & Ors

Factual and Procedural Background

The Plaintiff parties ("SKB") appealed a judgment by Judge Pumfrey dated 5th December 2003, which rejected their claim that the Defendant parties ("Apotex") infringed patent No. 2,297,550, held the patent invalid, and ordered its revocation. The patent had previously undergone litigation initiated by Company B ("BASF"), resulting in most claims being invalidated except two, which were later renumbered as claims 1 and 2 following an amendment restricting the patent's monopoly. The current proceedings concern the validity of these amended claims and whether they cover the process used by the Defendant.

The patent relates to crystalline forms of the pharmaceutical paroxetine hydrochloride, specifically focusing on the anhydrate form substantially free of bound organic solvent. The Plaintiff’s product, marketed under the trademark Seroxat, is in the hemihydrate form, protected by a separate patent. The dispute involves technical issues regarding different crystalline forms—hemihydrate, anhydrate, and solvates—and their preparation processes.

The patent in suit was applied for in 1996 and amended following earlier litigation. The claims focus on processes for preparing paroxetine hydrochloride anhydrate substantially free of isopropyl alcohol (IPA) or other bound organic solvents, involving crystallisation followed by displacement of bound solvent using a displacing agent.

The Defendants’ product involves making an IPA solvate, drying it to reduce IPA content, then treating it with acetone, heating, and vacuum drying. The parties dispute whether this process infringes the patent claims and whether the claims are valid in light of prior art and obviousness arguments.

Legal Issues Presented

1. Whether the patent claims 1 and 2, as amended, are valid in light of prior published documents, particularly UK patent application '407 and US patent No. 2,864,817 (the erythromycin patent).
2. Whether the prior art discloses the claimed invention either by anticipation (novelty) or obviousness.
3. Whether the Defendant’s process infringes the patent claims based on the construction of the term "displacing agent" and the scope of the claims.
4. Whether the claims are sufficiently clear and unambiguous to be valid or are invalid for insufficiency.

Arguments of the Parties

Appellant's Arguments (Plaintiff - SKB)

• The prior art, particularly '407, does not anticipate the claims because it does not clearly and unambiguously disclose a displacement step removing bound solvent from the solvate.
• The water slurry step in '407 is merely a washing step and not a solvent displacement step.
• The Defendant’s process using acetone as a displacing agent is not disclosed or covered by the patent claims.
• The claims should be construed purposively to exclude solvent removal solely by drying after treatment.
• The Defendants’ experimental evidence relied upon to show obviousness is contrived and involves steps not disclosed in the prior art.
• The claims are ambiguous and potentially insufficient if construed to cover solvent removal by drying.

Respondent's Arguments (Defendant - Apotex)

• The prior art '407 discloses the claimed invention either by anticipation or obviousness, including the displacement of solvent from the solvate.
• The water slurry step in '407 effects displacement of IPA from the crystals, not merely washing.
• The Defendant’s process, involving acetone treatment and drying, falls within the scope of the claims.
• The use of large amounts of IPA in the prior art is reasonable and would produce the anhydrate.
• The combination of Buxton & Lynch document and the erythromycin patent supports obviousness of the claimed process.
• The experimental steps taken by the Defendant are technically justified and within the scope of skilled man’s discretion.

Table of Precedents Cited

Court's Reasoning and Analysis

The court began by considering the prior art, focusing on UK patent application '407, which disclosed crystalline paroxetine hydrochloride forms including hemihydrate, anhydrate, and IPA solvate, and a process involving crystallisation and drying. The court examined whether '407 anticipated or rendered obvious the patent claims relating to the displacement of bound solvent from the solvate to produce anhydrate substantially free of bound solvent.

The court found that '407 did not clearly and unambiguously disclose a displacement step removing bound solvent. The water slurry step described in example 1 of '407 was more consistent with washing rather than solvent displacement. The skilled man reading '407 without hindsight would not have understood this step as effecting displacement. Thus, the claims were not anticipated by '407.

Regarding obviousness, the court rejected the argument that the skilled man would have made obvious modifications to the '407 process to achieve displacement, finding that the evidence of such obviousness was based on hindsight and contrived experiments involving additional steps not disclosed in the prior art. The court emphasized the principle against ex post facto analysis.

The court also rejected the "Bodmin point" argument that the process would have worked in remote locations producing anhydrate, finding the factual basis insufficient and speculative.

On the erythromycin patent, which disclosed a solvent displacement step in erythromycin preparation, the court held that it was not obvious to combine this with the Buxton & Lynch document to arrive at the invention. The skilled man would not have had knowledge of bound solvent in paroxetine or the displacement step, so the combination was an illegitimate mosaic and did not render the claims obvious.

Turning to claim construction, the court agreed with the trial judge that a "displacing agent" is an agent that displaces the solvent during the slurry stage, not during subsequent drying. The Defendant’s process, involving acetone treatment followed by drying, did not fall within the claims because the acetone was not acting as a displacing agent during slurry but rather solvent removal occurred during drying. The court rejected the broader construction urged by the Plaintiff.

The court acknowledged other points raised by the Defendant regarding insufficiency and ambiguity of claims but declined to decide on them as the finding of non-infringement was dispositive. However, the court noted that these points appeared to have considerable force, particularly concerning the ambiguous meaning of "solvate" and "anhydrate" and the standard of "conventional drying techniques."

Holding and Implications

The Court of Appeal reversed the trial judge’s finding that the patent claims were invalid for anticipation and obviousness over '407 and the erythromycin patent. The claims were held to be valid on these grounds.

However, the Court upheld the finding of non-infringement, concluding that the Defendant’s process did not fall within the scope of the patent claims as properly construed.

The direct consequence is that the patent remains valid but is not infringed by the Defendant’s process. The patent will be restored to the register. No new precedent was established beyond the application of existing principles on novelty, obviousness, claim construction, and expert evidence in patent litigation.