15 October 2020
In Singapore, pursuant to the Health Products (Therapeutic Products) Regulations 2016, applicants for registration of a therapeutic product in Singapore must declare whether "a patent is in force in respect of the therapeutic product" ("pertinent patent"). This requirement is part of a patent linkage scheme, which ensures that no therapeutic product is approved before expiration of the pertinent patent, except with the consent of the patent owner.
Whilst there was previously some uncertainty as to whether a process patent can be a pertinent patent, the Court of Appeal in Zyfas Medical Co v Millennium Pharmaceuticals, Inc. [2020] SGCA 84 has now confirmed that this is the case. As such, applicants for therapeutic product registration in Singapore should consider the need to declare, not only the product (or compound) patents for the active ingredients in the therapeutic products, but also process patents. The Court of Appeal appears to have suggested that a process patent needs to be declared so long as the active ingredient in the product could have been made using the patented process. The decision is expected to increase the burden on applicants seeking registration of therapeutic products in Singapore.
Background
The Singapore patent linkage scheme is set out in regulation 23 of the Health Products (Therapeutic Products) Regulations 2016 ("HPR"). Under this scheme, an applicant for registration of a therapeutic product in Singapore is required to declare to the Health Sciences Authority ("HSA") whether a patent is in force "in respect of the therapeutic product" and, if so, whether the patent is invalid or will not be infringed by the doing of the acts for which registration is sought. HSA may then direct the applicant to notify the patent owner of its application. Upon receipt of such notification, the patent owner may object to the registration by filing, within 44-days, an action in court for an injunction or a declaration that the patent is valid or will be infringed. Any court action will trigger a 30-month moratorium during which the HSA will not register the product, unless a final decision is rendered before the end of the 30-month period or parties settle the dispute.
In some jurisdictions, such as the US and Canada, the authorities maintain and publish a list of relevant patents (e.g., the "Orange Book" in the US), and therapeutic product applicants are only required to make declarations in relation to the patents found in the Orange Book or its equivalent. Notably, process patents are expressly excluded from the Orange Book. There is no equivalent of the Orange Book in Singapore. Instead, therapeutic product applicants are simply required to declare whether a patent is in force "in respect of the therapeutic product". This phrase is not defined in the HPR and the issue of its correct interpretation – in particular, whether it covers process patents – has been raised in a number of cases. The Court of Appeal in Zyfas Medical Co v Millennium Pharmaceuticals, Inc. [2020] SGCA 84 ("Zyfas") has now provided clarity on this issue.
A process patent can be a patent "in respect of the therapeutic product" under regulation 23 of the HPR
A summary of the facts and decisions in Zyfas is set out below.
High Court
In the High Court:
- Zyfas Medical Co ("Zyfas") had successfully obtained registration in Singapore of its generic drug "Myborte" containing the active ingredient bortezomib, a drug which is used in the treatment of multiple myeloma and mantle cell lymphoma.
- It appears that at the time Zyfas' filed its application for product registration, there was no product (or compound) patent for bortezomib in force in Singapore.
- Millennium Pharmaceuticals, Inc. ("Millennium") sought a Court Declaration under regulation 24(1)(a)(ii) of the HPR that Zyfas had, in applying for the registration, omitted to disclose "matter that is material to the application". This was on the basis that Zyfas had not filed HPR declarations in relation to three process patents owned by Millennium when making its application. The Court Declaration would enable Millennium to apply to the HSA for cancellation of Zyfas' registration.
- Zyfas contended that it did not knowingly or intentionally omit to declare the process patents. However, Zyfas conceded that a process patent could be a pertinent patent under regulation 23 of the HPR and that the existence of Millennium's process patents was a "matter that is material to the application".
- Based on its interpretation of regulation 24(1)(a)(ii) and in light of Zyfas' concessions, the High Court granted the Declaration sought by Millennium.
Court of Appeal
On appeal, Zyfas abandoned its previous argument (which was rejected by the High Court) that regulation 24(1)(a)(ii) HPR required a false or misleading statement or material omission in an HPR declaration to have been made knowingly or intentionally. Instead, Zyfas sought leave to argue, for the first time, that a process patent did not fall within regulation 23 HPR. The Court of Appeal ("CA") noted that leave would ordinarily have been refused given Zyfas' earlier contradictory concession, but allowed leave given the special circumstances of the case, including the fact that the issue would impact the implementation of the HPR and future applicants for therapeutic product registration.
Therefore, the CA had to consider whether "a patent in respect of the therapeutic product" under regulation 23 of the HPR included a process patent.
This is not the first time that the CA has opined on this particular issue. The earlier case of Millennium Pharmaceuticals, Inc v Drug Houses of Australia Pte Ltd [2019] SGCA 31 ("DHA") involved an action by Millennium seeking, among other things, a Court Declaration under regulation 24(1)(a)(ii) of the HPR that DHA had made a false declaration to HSA when applying for registration of its therapeutic product. Millennium alleged that DHA had failed to identify two of Millennium's process patents as pertinent patents. There was also a cross-application by DHA for Millennium's Statement of Claim to be struck out on the ground that it disclosed no reasonable cause of action. Although the High Court had earlier ruled in DHA's favour, the CA dismissed DHA's striking out application on the basis that DHA ought to have filed HPR declarations identifying Millennium's process patents, even if DHA had taken the position that it did not infringe those patents.
Zyfas submitted that the CA's holding in DHA was obiter dicta and, in any event, was wrong, and that the CA was not bound by its own decision.
The CA in Zyfas disagreed that its holding in DHA was obiter. It gave the following reasons for its conclusion that process patents fell within regulation 23 of the HPR:
- The plain text of the regulation suggested that process patents were included since "patent" under the Patents Act includes process patents.
- The inclusion of process patents was consonant with the legislative purpose of regulation 23 HPR, which was intended to give notice and protection to the patent proprietors, and there is no reason why product patents should be accorded more protection than process patents since a therapeutic product could infringe one or the other.
Zyfas had also argued that it would be onerous for an applicant to have to file the HPR declaration in relation to a process patent (as well as in relation to a product patent) and then have the HPR application held up by 30 months. This argument was also rejected, on the basis that the applicant could always shorten the wait by applying to court for a declaration of non-infringement.
In light of Zyfas' concession that it was "logically possible" for the bortezomib in Myborte to have been manufactured using the processes in Millennium's process patents, the CA concluded that the three process patents raised by Millennium fell within regulation 23 of the HPR because "the active ingredient in that product could have been made using the patented processes".
Commentary
How does an applicant identify a pertinent process patent?
The CA decision in Zyfas makes it clear that a process patent can be a pertinent patent under regulation 23 of the HPR. This means that process patents (in addition to product patents) must be taken into account when making the HPR declaration in support of a therapeutic product application. The question, then, is how is an applicant to go about searching for and identifying pertinent patents?
The CA's decision appears to suggest that a process patent ought to be declared as long as the active ingredient in the therapeutic product "could have been made" using the patented process. However, should this be the only criterion, considering that there can be a multitude of ways to produce many drug compounds?
It is often the case that process patents cover the gamut of processes used in the manufacturing of therapeutic products. As it is, there is a multitude of process patents on the Singapore patents register. As such, the number of patents covering processes by which any active pharmaceutical ingredient could have been made is potentially very large.
In Zyfas, Millennium was the proprietor of all the three process patents raised, and it is expressly mentioned in the descriptions of all the three patents that the patented processes may be used to manufacture bortezomib. In fact, all three patents also contain claims directed to processes for manufacturing a compound with a molecular structure which corresponds to that of bortezomib. It is unclear from the judgment if these factors had been relevant to the CA's decision that the three patents are pertinent patents that ought to have been declared, but that may well have been the case.
More clarity is needed to help therapeutic product applicants navigate the patent minefield
A recent search of the online register of Singapore patents for "patents in force" which are owned by Millennium revealed approximately 20 patents. Further, a search for Singapore patents in force which contain the term "bortezomib" in their abstracts and/or specifications revealed a total of approximately 240 patents, 6 of which belong to Millennium.
These numbers give a flavour of the difficulty faced by a therapeutic product applicant when trying to search for and identify a pertinent patent.
• The applicant could potentially have to wade through over a hundred patents in order to identify patents relating to processes by which the active ingredient (in this case bortezomib) could have been made.
• If the applicant is required to file HPR declarations in relation to all patents relating to all processes by which the active ingredient in the product could have been made, the applicant could potentially have to file over a hundred HPR declarations.
• It is difficult to imagine that this could have been the intention of either the legislature or the CA, given the undue burden that it would place on applicants.
This is particularly so given the High Court's decision in Zyfas (which the CA expressed agreement with) that a Court Declaration may be made under regulation 24(1)(a)(ii) of the HPR even if the omission to disclose a material matter was not made knowingly or intentionally. This means that the applicant bears the onus of identifying all pertinent patents, and any failure to declare a pertinent patent will give rise to the risk of any resulting registration being cancelled even if the applicant were unaware of the patent or had any inkling that it could be a pertinent patent.
There should be more clarity and guidance on which process patents may constitute pertinent patents under regulation 23 of the HPR. For example, should such patents be narrowed down to only patents which specifically refer to the relevant therapeutic product in the patent claims?
Legislative review needed to rebalance the scales
Under the current regime, the scales appear to be tilted in favour of patent owners. A patent owner who is notified of a therapeutic product application is able to hold up registration of the product for up to 30 months by seeking an injunction or a court declaration in relation to validity or prospective infringement, without having to defend the merits of the claims until the proceedings are in an advanced stage. Further, if the patent owner is not notified of a therapeutic product application (because the applicant did not file any HPR declaration in relation to his patent), he can seek a Court Declaration under regulation 24(1)(a)(ii) of the HPR that there was an omission to disclose a material matter, and rely on any Declaration made to apply to the HSA for the product registration to be cancelled.
In light of these issues, a thorough review of the relevant legislation (and a possible introduction of our own version of the Orange Book) appears to be warranted. The aim of the review would be to provide more clarity on the therapeutic product application process, such that whilst the interests of patent owners continue to be protected, a more level playing field may be provided for manufacturers of generic drugs or biosimilars, to enable access to affordable healthcare for the public after the compound patents for therapeutic products have expired.
