In Taiwan, after a brand drug company obtains a new drug license, it can proactively disclose invention patents related to the substance, formulation, or use of the new drug through the Patent Linkage System for pharmaceuticals, thereby linking the examination process of generic drugs to the patent status of the new drug. On the other hand, current examination practices for drug registration allow generic drugs to exclude certain indications approved for new drugs to avoid patent infringement disputes. This is known as the indication exclusion mechanism (a “carve-out”; the package insert after such exclusion is referred to as a “skinny label”).
Notwithstanding the above, is there a certainty that explicitly excluding the uses covered by a medical use invention patent from the indications specified on the generic drug approval may ensure avoidance of infringement of the medical use invention patent? The Intellectual Property and Commercial Court (hereinafter referred to as the IPC Court) held in Civil Judgment No. 9, 2021 that the evaluation should be based on “the therapeutic efficacy given to the disputed drug itself as derived from the human clinical trial results referenced in the complete package insert of the generic drug,” rather than solely relying on “the skinny labelof the generic drug.” Moreover, the Judgment emphasized the need to investigate whether, in medical practice, it is possible to distinguish the excluded indications from those listed in the skinny label of the generic drug. For the key points of this Judgment, please refer to our firm’s report published in April 2022. In October this year, the IPC Court adopted a similar approach as reflected in Civil Judgment No. 58, 2023, although the judgment in that case was in favor of the generic drug manufacturer. A brief overview is as follows.
In Civil Judgment No. 58, 2003 case, the disputed drug contains the same active ingredient as the patented brand drug (Nintedanib ethanesulfonate). Therefore, the key to determining whether a patent infringement has occurred lies in the relevance of the indications of the disputed drug to the disputed medical use invention patents (Invention Patents Nos. I268922, I285635, and I418351). Since the disputed drug has not yet been approved for marketing, the IPC Court pointed out that the drafts of the package inserts for the disputed drug hold significant reference value in determining whether it falls within the scope of the disputed patents or the scope of their approved patent term extensions.
According to the draft of the package insert, the indication for the disputed drug is “Progressive Fibrosing Interstitial Lung Disease (PF-ILD).” As for the disputed patents, they pertain to the treatment of “Idiopathic Pulmonary Fibrosis (IPF)" and "Scleroderma-Associated Interstitial Lung Disease (SSc-ILD).”
The IPC Court held that PF-ILD in the disputed drug can be clearly distinguished from IPF and SSc-ILD in the disputed patents not only in “clinical diagnosis and treatment practice” but also in “clinical drug trials.” Therefore, PF-ILD falls outside the scope of the disputed patents. The reasoning is as follows:
- Viewed from clinical diagnosis and treatment practices:
According to the pharmaceutical benefit regulations of the National Health Insurance (NHI), the reimbursement criteria for the active ingredient of the disputed drug to treat PF-ILD are different from those for the two indications covered by the disputed patents. The main distinction lies in that the reimbursement criteria of PF-ILD require evidence of pulmonary function deterioration accompanied by worsening respiratory symptoms or increased fibrosis as confirmed by high-resolution computed tomography (HRCT) scans. Therefore, in clinical diagnosis and treatment practices, PF-ILD can be clearly distinguished from IPF and SSc-ILD.
Although the plaintiff argued that some or all patients with IPF or SSc-ILD may progress to PF-ILD, resulting in an overlapping, the IPC Court held that clinical physicians, at the time of diagnosis, can indeed use tools such as HRCT imaging and pulmonary function tests to differentiate PF-ILD patient groups from those with IPF or SSc-ILD. This demonstrates that in clinical practice, determining which of the three indications a patient belongs to does not lead to the confusion claimed by the plaintiff.
- Viewed from drug clinical trials:
The draft package insert for the disputed drug does not cite the clinical trial results for the treatment of IPF or SSc-ILD. The patients recruited to participate in the clinical trials cited were all clinically diagnosed with PF-ILD, explicitly excluding IPF patients. These trials demonstrated that the disputed drug has significant therapeutic effects on such patients and can reduce the risk of mortality. Accordingly, it can be confirmed that the disputed drug is indeed effective for the treatment of PF-ILD as indicated in its draft package insert and that the indication for the disputed drug is supported by the human clinical trial results cited in the draft package insert. The exclusion of the indications covered by the disputed patents is thus also medically reasonable.
The IPC Court disagreed with the plaintiff’s assertion that “the defendant’s removal of the indications from Sections 1-- Pharmacokinetics, 5-- Warnings and Precautions, 6-- Special Populations, 8.2-- Clinical Trials Experience, and 9-- Overdosage in the package insert does not change the fact that the trial results cited were obtained from clinical trials conducted on IPF or SSc-ILD patients and can be applied to IPF or SSc-ILD.” The Court pointed out that these Sections primarily discuss pharmacokinetic similarities among different patient groups, side effects/adverse reactions and safety observed after drug administration, and the lack of overall efficacy and safety differences between elderly and younger trial participants. These points are all unrelated to the therapeutic efficacy of Nintedanib for the treatment of IPF, SSc-ILD, or PF-ILD.
On the other hand, in response to the plaintiff’s argument that “off-label use” is a common prescribing practice among physicians, which raises the risk of patent infringement caused by the disputed drug, the IPC Court pointed out as follows:
The package insert serves as a guideline for clinical medical or pharmaceutical personnel, and physicians are expected to prescribe medication to patients based on the indications listed in the package insert. Former judgments have also held that off-label use is the personal action of the physician and is unrelated to the determination of patent infringement (refer to the reasoning in Civil Judgment No. 38, 2023). Moreover, information regarding the eligibility of off-label use for drug injury relief is likewise unrelated to whether the disputed drug constitutes patent infringement.
Off-label use is not covered by National Health Insurance (NHI); therefore, in principle, physicians would not prescribe the disputed drug, which is not covered by NHI when it is designated for use in treating IPF or SSc-ILD, to patients diagnosed with IPF or SSc-ILD. Furthermore, if a patient is diagnosed with IPF or SSc-ILD, he/she can receive NHI reimbursement for the patented brand drug, making it unlikely that the patient would opt to pay out of pocket for the disputed drug. Conversely, if the patient does not meet the NHI reimbursement criteria, it indicates that he/she has not been diagnosed with IPF or SSc-ILD. In such cases, a physician prescribing the disputed drug to the patient for self-paid use does not constitute patent infringement.
It appears, from the aforementioned Judgment, that in determining whether the package insert of a generic drug, after indication exclusion, falls within the scope of a use patent, the court would comprehensively consider if the two drugs of concern can be clearly distinguished in clinical diagnosis and treatment practice. National Health Insurance reimbursement standards serve as an objective criterion for such determination. Furthermore, whether the clinical trials cited in the generic drug’s package insert can support the corresponding efficacy with medical reasonableness is also a key factor. The Judgment is a first-instance decision, while the plaintiff has filed an appeal. Our firm will continue to monitor subsequent developments and provide timely updates.