The Marketing Approval and “Patents Linkage” System in Singapore
The marketing approval process is governed by the Singapore Health Sciences Authority (HSA), under the Health Products (Therapeutic Products) Regulations 2016 (TPR), which also sets out the applicant’s obligations under the patents linkage scheme and provides legal basis for regulatory data exclusivity.
An applicant for approval of any drug must declare to the HSA whether there are any patents in force that relate to the product in question. The applicant must also declare to the HSA that:
a) the patent owner has given consent (to the launch of the generic version);
b) the patent is invalid; or
c) the patent will not be infringed by acts relating to the therapeutic product.
The consequence of filing a declaration that contains false information include a fine and/or imprisonment of up to 12 months, so it is important for a generic competitor to diligently list any and all patents (including process patents) that may be relevant to the product they wish to launch.
If the generic company applies for marketing authorisation in the last 18-months of the patent’s life, with an indication that the approval should be dated after the patent has expired, then the marketing approval process will continue unabated. In any other case where the existence of a patent is declared and patentee has not consented to the marketing authorisation application, the HSA will issue a notice requiring the generic company to serve notice on the patentee, stating that they have applied for marketing approval.
Upon service of notice to the patentee, the marketing approval process is halted for a period of 45 days to allow time for the patentee to apply to the court to block the approval or to obtain a declaration that the patent is valid and would be infringed. If no application to the court is made during the 45 day period, the marketing approval process continues unabated. However, the registration process will be suspended for up to 30-months (total delay of up to 31.5 months) if the patentee challenges the proposed registration. This delay in proceedings is intended to provide sufficient time for the courts to consider the facts and arrive at a conclusion. In the unlikely event that a decision has not been reached by the courts within 30 months, the generic company can then continue with the approvals process while awaiting the conclusion of the court case. If the court case concludes in the favour of the generic company within 30-months, then they can apply to the court to overturn the stay in proceedings. However, if the patentee wins, then the generic will need to wait until closer to the expiration date of the patent before trying to register their product.
The procedure above can lead to uncertainty for both the generics company, as well as the patentee. For example, should the patentee apply to the court if they cannot determine whether a generic product falls within the scope of their patent within the 45-day period? On the other hand, does a generics company have to declare the existence of a process patent when they will manufacture the drug by a different process? Both of these issues are discussed below with reference to case law in Singapore.
Identity of Generic Product Unclear
Can a patentee use the patent linkage scheme to block a generic competitor when they are unsure of infringement? This issue was considered by the Singapore High Court in AstraZenaca AB v Sanofi-Aventis Singapore Pte Ltd  SGHC 16.
This case was decided under the old Medicines Act, which was replaced by the TPR in 2016. However, the provisions of the Medicines Act that were relied upon are essentially identical to those in the TPR and so it appears highly likely that the same outcome would occur under the TPR.
Sanofi-Aventis (Sanofi) sought marketing approval for certain film-coated tablets comprising rosuvastatin and a stabiliser. They declared that the products would not infringe AstraZeneca’s Singapore Patent No. SG 89993 (‘993) because their proposed composition did not comprise an “inorganic salt in which the cation is multivalent”, as set out in the patent claims.
AstraZeneca had two important decisions to make in 45 days. First, did they have sufficient basis to apply to the court when they did not have enough information to know whether Sanofi’s product would infringe their patent? Secondly, what should they rely on for “infringement” – the Patents Act or the Medicines Act?
AstraZeneca applied to the court within the specified 45 days under the Medicines Act for a declaration that the ‘993 patent would be infringed by Sanofi’s product, and sought an injunction to restrain Sanofi from performing acts that would infringe the ‘993 patent. AstraZeneca chose the Medicines Act as the basis for their suit due to concerns that the Patents Act requires an infringing act to have been committed before infringement proceedings can begin. In contrast, the Medicines Act only requires that a prospect of future infringement needs to be established for their case to succeed (i.e. approval would result in the launch of an infringing product). The court approved the use of the provisions of the Medicines Act in this context.
AstraZeneca argued that they did not believe that the Sanofi product fell outside the scope of the patent. This is because AstraZeneca did not believe it possible to produce a stable formulation of rosuvastatin that fell outside their patent claims. They also argued that their application to the court was reasonable given that they only had 45 days to bring proceedings to benefit from the 30-month stay on the marketing approval and that it was not possible to obtain all of the evidence in this time-frame, especially as Sanofi had not disclosed full details of their product. Sanofi sought to have the claim struck out on the basis that AstraZeneca were unable to provide evidence of infringement.
While mere belief of infringement would probably not be sufficient to bring proceedings under the Patents Act, the court held that the Medicines Act was intended to cover this scenario and so the level of information provided in the initial claim was acceptable. AstraZeneca sought discovery in respect of Sanofi’s specific products, on the basis that it needed this information to properly assess infringement. Discovery was granted and Sanofi had to disclose the composition of their product, although appropriate confidentiality provisions were put in place.
As is clear from the above, the patentee can start proceedings without a clear idea of whether the product will infringe the patent(s) in question. However, further evidence will need to be obtained during the proceedings, which could be through the voluntary sharing of information by the generic to exclude infringement or by discovery. This appears to be a balanced approach, given the short period of time available to the patentee to start proceedings under the TPR (or formerly, the Medicines Act).
What Constitutes a “relevant” Patent that must be Disclosed?
Certain issues relating to marketing approval and when a patent is relevant are dealt with in Millennium Pharmaceuticals, Inc. v Drug Houses of Australia Pte Ltd  SGHC 149 (first instance) and the subsequent appeal  SGCA 31. The full trial has not been heard, and both of these judgements relate to applications to strike out certain claims.
Millennium Pharmaceuticals (Millennium) are the proprietor of Singapore patent nos. SG 151322 and SG 182998 (the patents), both of which relate to processes for the manufacture of the anti-cancer drug bortezomib.
Drug Houses of Australia (DHA) obtained marketing approval in Singapore for a product containing bortezomib. Although the declaration filed as part of DHA’s application process was never made available, the Court of Appeal concluded that, “…it can be fairly implied that the Respondent did not declare the existence of the Appellant’s two patent’s to the Health Sciences Authority…”. This meant that Millennium was not served notice that DHA had applied for marketing approval and were not able to halt the approval process by commencing litigation under the TPR. DHA asserted that they did not use the processes disclosed in the patents, and accordingly that there was no need to declare their existence to the HSA.
Millennium applied to the High Court for a number of remedies, including:
- an order that by failing to declare the existence of the patents, DHA had filed a declaration containing a material falsehood (obtaining such an order would enable Millennium to apply for the granted marketing approval to be revoked);
- a declaration that DHA’s performance of the acts for which their products had been registered would constitute infringement of the patents; and
- an injunction to restrain DHA from infringing the patents.
DHA applied to have these claims struck out. As they had not been notified by DHA, Millennium could not rely on the provisions discussed above. Instead, they based their claim on a different provision in the TPR, which allows any interested person to apply for cancellation of the marketing approval if doing an act authorised by the marketing approval “infringes a patent under the Patents Act”. The first instance decision held that the reference to the Patents Act meant that a claim could only be based on a past act of infringement (which had not occurred). On this basis, it was deemed impossible for claims (ii) and (iii) to succeed, and they were struck out. The first instance court concluded that the reference to the Patents Act should be interpreted in this way because otherwise a proprietor who missed the 45-day window to bring proceedings would have another opportunity after the marketing authorisation’s grant, even when no infringement had occurred.
The Court of Appeal disagreed. In their decision, they opined that the TPR is not necessarily concerned with proving actual infringement of a patent. Rather, it considers whether an act authorised by a marketing approval would infringe a patent, irrespective of whether the act has taken place or not. Whether this means that a patentee gets a second chance at using the TPR, they noted that a proprietor who does not take action when made aware of an application for marketing approval risks the market being flooded with cheap generic products: “There is no abuse in the proprietor now wanting to have the registration cancelled if he can obtain a determination on the specified matters”. As a result, and while not necessarily agreeing that Millennium’s case would ultimately succeed at full trial, they deemed that Millenium’s claims should not be struck out.
More generally, the Court of Appeal noted that a generic company cannot omit a process patent from their declaration simply because they intend to use a different process. Instead, a generic company “has to declare the patents and then state, among several possibilities, that the patents are invalid or will not be infringed…” It is for the Singapore authorities to decide whether notice must be served on the proprietor.
Thus, the message to generics companies is clear: declare all patents which could be considered relevant to your product (including processes), even where you are sure that you will not infringe them.
Other Methods to Delay Generic Entry to the Market
Three further options are available to delay market entry of generics onto the Singapore market- though only one of these relates to the marketing approval process.
Singapore has a data-exclusivity provision in the TPR of 5 years from the date of the original marketing approval, which means that the HSA will not grant approval for a generic drug based the original test data without approval of the originator company. This protection is automatically available and guarantees at least a short monopoly period for innovator companies.
Patent Term Extensions (PTEs) and Adjustments (PTAs) are available in Singapore and are based on the equivalent provisions of US patent law. However, PTEs are typically hard to obtain in Singapore because only delays attributable to the HSA are considered when determining whether there has been an “undue delay” in granting the MA. Given that the HSA usually grants marketing approval quickly, PTE is unlikely unless the first marketing approval is obtained in Singapore. PTAs are possible due to delays in prosecution by the Singapore Patent Office or by a foreign patent office that has a similar scheme (e.g. the USPTO). The latter may be easier to obtain if one uses modified examination to obtain grant of a patent in Singapore, but it is difficult to obtain the former due to the way that the Adjustment is calculated by the Singapore Patent Office.
As is evident from the above, the patent linkage scheme is generally favourable to innovator companies because the generic competitor is required to inform the innovator of any patents that might be infringed, and the innovator can bring proceedings (and hence the delay) before they are sure that there is an infringement. This highlights the importance of formulation, dosage regime and process patents in Singapore, each of which could be used to delay generic entry to the market after the expiry of an original product patent. In contrast, there is a heavy burden on generics companies to declare all patents relevant to their generic product. Failure to comply can lead to marketing authorisation being revoked and even criminal sanctions for the people responsible.