Millennium Pharmaceuticals, Inc. & Anor v Zyfas Medical Co (Sued as a firm)

Facts

Millennium Pharmaceuticals, Inc, the registered proprietor of two Singapore process patents for making bortezomib, a cancer drug used against multiple myeloma and mantle cell lymphoma, sued Zyfas Medical Co, a Singapore partnership that distributes medicines, in Suit No 817 of 2019. Johnson & Johnson Pte Ltd, which distributes the branded drug Velcade in Singapore, was joined as second plaintiff on the basis that it was an exclusive licensee. Bortezomib itself is not patent-protected in Singapore, so the dispute concerned only the manufacturing processes.

The first patent, SG 322, teaches carrying out a key step of the Matteson homologation reaction in an ether solvent of low miscibility with water, such as MTBE, to reduce epimerisation, an impurity problem made worse by moisture. The second, SG 29P, claims a convergent synthesis of bortezomib. Zyfas obtained Health Sciences Authority registration for a generic bortezomib made by Dr Reddy's Laboratories (DRL) in India and supplied 2,183 vials to public hospitals under a tender. The plaintiffs alleged that importing and supplying this product infringed both patents. Zyfas denied infringement, saying DRL used THF, a water-miscible solvent, and counterclaimed that the patents were invalid. Liability was tried separately from any assessment of damages, with a court assessor assisting on the technical evidence. Related proceedings had earlier found that Zyfas omitted the patents from its regulatory declarations, and the HSA cancelled the product's registration on 27 August 2021.

Issues

1. Whether Johnson & Johnson Pte Ltd had standing to sue as an exclusive licensee.
2. Whether claim 1 of SG 322 was novel, inventive and sufficiently disclosed.
3. Whether SG 29P was invalid for lack of novelty or inventive step.
4. Whether the burden of proof shifted to the defendant under s 68(1) of the Patents Act, and whether DRL's process infringed SG 322.

Holding

Dedar Singh Gill J dismissed the plaintiffs' claims, while the defendant's counterclaim succeeded in part. The second plaintiff had no standing. On the counterclaim, SG 29P was held invalid for lack of inventive step, while SG 322 was held valid because the limb of claim 1 using a low-miscibility ether solvent with a coordinating co-solvent was novel and inventive, even though the limb using such a solvent alone lacked novelty and inventive step. SG 322 was not shown to be infringed by DRL's process. Costs were awarded to the defendant, to be agreed or taxed.

Reasoning

On standing, the court did not need to decide whether an exclusive distributor can be an exclusive licensee. The plaintiffs produced none of the licence or distribution agreements, the second plaintiff's legal director accepted under cross-examination that it was not the exclusive licensee, and the licence was not registered in any event.

On SG 322, the judge rejected the plaintiffs' attempt to treat literature they accepted as common general knowledge as outside the state of the art. An earlier patent, US 309, listed diethyl ether, petroleum ether "and the like" as solvents, and the plaintiffs' expert accepted this would include MTBE, so the single-solvent limb was anticipated and obvious to try. Nothing in the prior art, however, pointed to mixing such a solvent with a coordinating co-solvent in the claimed proportions, so that limb, and claim 1, survived. A wrong cross-reference in claim 12 was an obvious error a skilled reader would correct, so the claim was not insufficient.

On SG 29P, linear and convergent synthesis were both common general knowledge, and two earlier patents (WO 506 and WO 507) used convergent synthesis for analogous boronic acids. With a fair expectation of success, convergent synthesis of bortezomib was obvious to try. A textbook warning about enantiomerisation did not amount to a technical prejudice. The dependent claims fell with claim 1.

On infringement, the burden did not shift. The plaintiffs relied on theory, arguing that DRL could not reach its reported purity using THF, but DRL's documents showed moisture limits and anhydrous reagents, a laboratory report measured diastereomer impurities in a sample at about 0.05%, and the prior art showed other ways to make bortezomib. The plaintiffs also failed to make reasonable efforts to find out DRL's process: they called no witness from the first plaintiff and declined an offer to visit DRL's factory, giving COVID-19 as the reason. Both the plaintiffs' witness and counsel accepted that if MTBE was not used there was no infringement, and the court found it was not shown to be used.

From the judgment