Background
Patent term extension (PTE) is a form of compensation for time taken to obtain government approval for pharmaceuticals and agrochemicals required prior to exploiting the patent. This compensation was first introduced into Taiwan in 1994. In the amendments to the Patent Act published in 2011 and implemented in 2013, a limitation of the effective ingredients and use was introduced to restrict the patent scope during the extension period¹.  The legislative reasons of this limitation indicate that “the scope of a patent during the extension period shall be limited to only the claimed product, use or manufacture process corresponding to the effective ingredients and use stated in the regulatory approval [based on which the PTE is requested] and should not encompass other products, uses or manufacture processes which are described in the claims but the effective ingredients and use are not stated in the regulatory approval [based on which the PTE is requested].” However, there are different interpretations about this limitation: whether this stipulation is an absolute limitation on the patent scope during the extension period, or this stipulation merely sets a rule on how the patent scope during the extension period should be interpreted based on the original patent scope. With respect to pharmaceuticals, advocates of the former interpretation believe that the patent scope during the extension period should be limited to the exact combination of the active ingredient(s) and indication(s) stated in the marketing approval (MA) based on which the PTE is requested, i.e., any variations such as an additional ingredient or an additional indication (even if the additional indication is related to that stated in the MA based on which the PTE is requested) would prevent another drug from infringing the patent right during the extension period. On the other hand, advocates of the latter interpretation consider that drugs with such variations may not escape from infringing the patent right during the extension period if they are covered by the original patent scope and involve the active ingredients and the medical use stated in the MA.

In 2024, two judgments concerning the indication carve-out under the patent linkage system to avoid infringing patent rights during the extension period of PTE²  were rendered. The court considered that medical reasonability in view of the clinical trials conducted to obtain the MA based on which the PTE is requested, clinical practices for the indications, and the scope of benefits of the National Health Insurance should be taken into consideration when determining whether an indication may be carved out during the extension period³.  Nonetheless, these two judgements focus on whether the carve-out is medically reasonable and do not dwell on the interpretations of the patent scope during the extension period per se, which were firstly discussed in another recent litigation, Merck Sharp & Dohme LLC v. Anxo Pharmaceutical Co., Ltd⁴. 

Facts
The patent of concern TWI226331 is owned by Merck Sharp & Dohme LLC and protects compounds in Markush claims covering the active ingredient sitagliptin and its pharmaceutically acceptable salts. The patent was scheduled to expire on July 4, 2022. Later, the patent term was extended to January 9, 2025 based on the MA of Januvia, of which the active ingredient is sitagliptin (as monohydrate phosphate salt), and the indication is type 2 diabetes mellitus. The patent scope during the extension period is sitagliptin (as monohydrate phosphate salt) for use in type 2 diabetes mellitus. Afterwards, Merck Sharp & Dohme obtained another MA for Janumet, a combination tablet with sitagliptin phosphate (as monohydrate phosphate salt) and metformin hydrochloride as the active ingredients indicated as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus patients who:
-    have received combinational therapy of sitagliptin and metformin; or 
-    have received either sitagliptin or metformin alone but the control is inefficient; or
-    have received combinational therapy of metformin and sulfonylurea but the control is inefficient; or 
-    have received combinational therapy of metformin and a PPARγ agonist but the control is inefficient; or
-    have received combinational therapy of metformin and insulin but the control is inefficient.

TWI226331 is listed under the MA of Janumet in the patent linkage system. In January 2024, Anxo Pharmaceutical Co., Ltd. filed an abbreviated new drug application for the generic version of Janumet, Gluphor, and submitted a Paragraph IV Certification of non-infringing the patent right of TWI226331. After receiving the notification of the certification from Anxo Pharmaceutical Co., Ltd., Merck Sharp & Dohme LLC sued Anxo Pharmaceutical Co., Ltd. for infringing the patent right of TWI226331.

Main Issue
The main issue of the litigation resided in how the patent scope of TWI226331 during the extension period “sitagliptin (as monohydrate phosphate salt) for use in type 2 diabetes mellitus” should be interpreted. Are the elements of the active ingredient “sitagliptin (as monohydrate phosphate salt)” and the indication “type 2 diabetes mellitus” strict, exclusive, close-ended limitations, or are they merely open-ended features limiting various compounds within the scope of the Markush claims of the original patent scope of TWI226331 to “sitagliptin (as monohydrate phosphate salt)” and limiting the medical use to conditions relevant to “type 2 diabetes mellitus”?

During the litigation, Anxo Pharmaceutical Co., Ltd. argued against the infringement based on the legislative reasons of the patent scope limitation during the extension period of PTE, along with statements emphasizing the following aspects:

1. Active Ingredients
The active ingredients of Gluphor, sitagliptin phosphate (as monohydrate phosphate salt) and metformin hydrochloride in combination, are not identical to sitagliptin (as monohydrate phosphate salt), the active ingredient protected by the patent scope of TWI226331 during the extension period. Additional clinical trials are required to obtain the MA for a combination tablet.

2. Indications
The second-line therapy of Gluphor, type 2 diabetes mellitus patients who have received sitagliptin alone but the control is inefficient, contradicts the first-line therapy for treating type 2 diabetes mellitus with sitagliptin (the indication protected by the patent scope of TWI226331 during the extension period). Additional clinical trials are required to obtain the MA for the second-line therapy for type 2 diabetes mellitus.

3. Rule of Dedication
An invention which is not covered by the patent scope during the extension period should be deemed dedicated to the public.

In the judgement, the court held that the legislative reasons merely set a rule on how the patent scope during the extension period should be interpreted based on the original patent scope rather than an absolute limitation on the patent scope during the extension period. Accordingly, the court objected to the defendant’s arguments with the following main reasons. 

1. Active Ingredients
The patent scope during the extension period should be interpreted case-by-case. Indeed, the compounds covered by the Markush claims of TWI226331 other than sitagliptin (as monohydrate phosphate salt) were excluded from the patent scope of TWI226331 during the extension period. However, if the purpose of statute to compensate for the time taken to obtain government approval required prior to exploiting the patent is met, a drug with an additional active ingredient in combination with sitagliptin (as monohydrate phosphate salt) should also be encompassed by the patent scope during the extension period. 

Furthermore, the clinical trials for Januvia also support the therapeutic effect of sitagliptin in combination with metformin. No clinical trials were conducted for Gluphor regarding the combination tablet of sitagliptin and metformin. Instead, only bioequivalence studies were conducted for Gluphor to demonstrate the equivalent effect of the combination tablet to the combination of a sitagliptin tablet and a metformin tablet. Accordingly, it is unnecessary to conduct additional clinical trials for the combination tablet with sitagliptin (as monohydrate phosphate salt) and metformin hydrochloride as the active ingredients with respect to relevant indications.

2. Indications
The therapy for “type 2 diabetes mellitus patients who have received sitagliptin alone but the control is inefficient” is not the only indication of Gluphor.

In fact, the package insert of Januvia indeed lists clinical trials of the first- and second-line therapies to support the indication of a generic concept, “type 2 diabetes mellitus,” the indication protected by the patent scope of TWI226331 during the extension period. The draft of package insert of Gluphor also cites the clinical trials from Januvia to support its therapeutic effects on type 2 diabetes mellitus patients who:
-    have received combinational therapy of sitagliptin and metformin; or 
-    have received metformin alone but the control is inefficient; or
-    have received combinational therapy of metformin and sulfonylurea but the control is inefficient.
Accordingly, Gluphor indeed falls within the patent scope of TWI226331 during the extension period with respect to these indications.

3. Rule of Dedication
The rule of dedication is a limiting factor for the doctrine of equivalents. However, the patent scope during the extension period reads on the product Gluphor, and thus it is unnecessary to consider the rule of dedication.

Conclusion
The court decided that Gluphor infringed the patent right of TWI226331 during the extension period, i.e., “sitagliptin (as monohydrate phosphate salt) for use in treating type 2 diabetes mellitus.” Most importantly, considering the original patent scope and the purpose of statute to compensate for the time taken to obtain government approval required prior to exploiting the patent, it is possible for the patent scope during the extension period to encompass active ingredients in addition to those specified in the MA based on which the PTE is requested, or relevant indications even if they are not literally stated in such MA. Although this is not a judgement rendered by the Supreme Court, it provides a preliminary perspective from the court regarding the interpretation of the patent scope during the extension period.

Notes: