In recent years, the incidence of thyroid diseases in China has shown a rapid upward trend, with the number of patients exceeding 200 million. In the treatment of thyroid diseases, levothyroxine sodium drugs play an indispensable role. Among them, Euthyrox, produced by German company Merck, has captured the major market share in China due to its affordable price and stable efficacy, becoming a daily medication for many patients.
However, as an imported drug, the stability of Euthyrox's supply chain directly affects the welfare of numerous domestic patients. Around 2016, Euthyrox experienced a shortage that affected the entire country, leaving many patients temporarily facing a situation without medicine available. This incident highlighted the potential risks of relying on a single imported drug.
Therefore, from a broader strategic perspective, China needs to possess self-developed and self-produced levothyroxine sodium drugs to ensure stable and reliable drug supply for domestic thyroid disease patients, particularly thyroid cancer patients, during special periods, forming a "backup" domestic drug defense line.
Fortunately, whether it is the world's earliest levothyroxine sodium originator drug—Synthroid® launched by Abbott Laboratories in 1955 in the United States, or Euthyrox launched by Merck in 1973—both have long exceeded their patent protection periods today, giving more companies the opportunity to develop levothyroxine sodium drugs.
However, Merck has now adjusted the formulation of its levothyroxine sodium product and applied for patent protection. Although Merck has invested in building a factory in Nantong, Jiangsu Province, and is gradually advancing the localization of Euthyrox production in China, its application for a new formulation patent may potentially impact the research, development and market launch of other similar generic drugs, further increasing the complexity of future drug supply and market competition. This series of developments further highlights the urgency and importance of accelerating the research, development and production of domestic levothyroxine sodium.
Recently, after undergoing three levels of review by the China National Intellectual Property Administration, the Beijing Intellectual Property Court, and the Supreme People's Court of China, the invention patent "Solid Pharmaceutical Preparation Containing Levothyroxine" (Patent No.: 201380042787.1), held by Merck Patent GmbH of Germany and belonging to the same type as its best-selling thyroid treatment drug Euthyrox, was ultimately declared completely invalid. This case not only highlights the strict requirements of patent law regarding inventive step, but also demonstrates Sunshine IP's professional capabilities in handling complex pharmaceutical patent disputes.
Claims
The claims of Merck's invention patent "Solid Pharmaceutical Preparation Containing Levothyroxine" define in Claim 1 a solid pharmaceutical preparation comprising levothyroxine sodium, gelatin (1-10% by weight), citric acid (0.1-3% by weight), mannitol (50-80% by weight), and corn starch (10-30% by weight). Merck claims that this formulation has "improved storage stability". The patent was granted on January 10, 2020, with a priority date of August 20, 2012.
Invalidation Challenge
In 2020, Sunshine IP was commissioned to file an invalidation request with the China National Intellectual Property Administration. The primary grounds for invalidation were that Claims 1-23 of the patent lacked inventive step as stipulated in Paragraph 3, Article 22 of the Patent Law of the People's Republic of China (as amended in 2008).
Sunshine IP's core arguments focused on prior art, particularly Evidence 1 (PCT Application Publication Document No. WO95/20954A1) and Evidence 2 (Chinese Invention Patent Application Publication Document No. CN1301148A). Evidence 1 disclosed tablets containing levothyroxine, citric acid, and corn starch, and mentioned that mannitol could be used as a filler and gelatin as a adhesive. Evidence 2 indicated that when gelatin was used as a adhesive in levothyroxine sodium preparations, the preparations exhibited "unexpected stability".
Invalidation Declaration
After reviewing the evidence and our arguments, the China National Intellectual Property Administration issued Invalidation Review Decision No. 48315, declaring the patent rights completely invalid. The China National Intellectual Property Administration determined that compared to Embodiment 1 of Evidence 1, the distinguishing features of Claim 1 mainly comprised the inclusion of 1-10% by weight of gelatin and 50-80% by weight of mannitol. It was determined that the actual technical problem solved was to provide a levothyroxine sodium solid pharmaceutical preparation with improved stability.
However, the China National Intellectual Property Administration held that a person skilled in the art could have arrived at the technical solution of Claim 1 through obvious combination of Evidence 1 (which taught that mannitol could be used as a filler with partially overlapping dosage ranges), Evidence 2 (which taught the use of gelatin to achieve stability), and common general knowledge. Therefore, Claim 1 lacked inventive step.
Merck was dissatisfied and filed a lawsuit with the Beijing Intellectual Property Court. The defendant argued that the China National Intellectual Property Administration had erroneously identified the distinguishing features, that there was a synergistic effect between citric acid, gelatin, and mannitol, and that citric acid was a stability enhancer rather than a destabilizer. Merck also contested the identified technical problem and asserted that unexpected technical effects had been achieved.
In its (2021) Jing 73 Xing Chu No. 14145 Judgment, the Beijing Intellectual Property Court upheld the decision of the China National Intellectual Property Administration. The court held that citric acid was not a distinguishing feature because Evidence 1 had already disclosed citric acid with a content falling within the range defined in Claim 1. The court further noted that Merck’s patent specification did not contain sufficient evidence to support the alleged synergistic effect, nor could it prove that gelatin and mannitol could change citric acid's effect from destabilizing to enhancing stability. The court agreed with the China National Intellectual Property Administration's conclusion that Claim 1 lacked inventive step.
Final Ruling
Merck appealed the case to the Supreme People's Court of China. Sunshine IP continued to represent the client and vigorously defended the earlier ruling.
In its final judgment (2023) Zui Gao Fa Zhi Xing Zhong No. 271 issued on May 22, 2025, the Supreme People's Court of China reviewed Merck's grounds of appeal item by item:
1. Closest Prior Art: Merck argued that Evidence 1 was unsuitable as the closest prior art due to different technical problems and subsequent stability requirements imposed by the U.S. Food and Drug Administration. The Supreme People's Court of China held that Evidence 1 was suitable as the closest prior art, noting that improving the stability of pharmaceutical preparations was a universal pursuit, and that judgment should be made based on the time point of this patent's priority date.
2. Distinguishing Features: Merck reiterated that citric acid, gelatin, and/or mannitol should be regarded as an integrated distinguishing feature due to synergistic effects. The Supreme People's Court of China supported the first-instance court's view: Evidence 1 had already disclosed that its pharmaceutical preparation contained citric acid, and the weight percentage fell within the numerical range defined in Claim 1 of this patent. Therefore, it was not improper to not identify the citric acid component as a distinguishing feature. This determination did not preclude considering the impact of distinguishing features on other technical features and the resulting synergistic effects when determining the actual technical problem solved by the invention.
3. Actual Technical Problem Solved: Merck argued that the actual technical problem solved by Claim 1 was how to convert citric acid from being detrimental to stability to improving stability, and to improve the stability of the preparation, in the presence of gelatin and/or mannitol. The Supreme People’s Court of China held that the specification of the patent in question did not indicate the influence of the presence of gelatin and/or mannitol on the stability effect exerted by citric acid, and therefore failed to demonstrate that citric acid and gelatin and/or mannitol exhibited a synergistic effect in enhancing stability. The supplementary experimental data submitted by Merck during the invalidation proceedings (Counter-Evidence 1) was deemed inadmissible, because the facts that Counter-Evidence 1 sought to directly prove were neither explicitly recorded nor implicitly disclosed in the original patent application documents. Consequently, the actual technical problem solved was correctly determined to be providing a solid pharmaceutical formulation of levothyroxine sodium with improved stability.
4. Technical Teaching or Suggestion: Merck argued that lactose in prior art provided far superior stability compared to mannitol, and that a person skilled in the art would have no motivation to replace lactose with mannitol, and would consider removing citric acid from Evidence 1. The Supreme People's Court of China held that Evidence 1 disclosed that levothyroxine tablets could contain mannitol as an inert filler and gelatin as a adhesive, and Evidence 2 further disclosed the addition of gelatin as a adhesive in levothyroxine sodium. Therefore, the prior art had already provided technical teaching or suggestion. Citric acid was not a distinguishing feature and should not be considered when judging technical teaching or suggestion.
5. Long-Unsolved Technical Problem and Unexpected Technical Effect: Merck argued that it had solved a technical problem that people had long been eager to solve but had never succeeded in, taking its product Euthyrox® as an example. The Supreme People's Court of China held that Merck failed to effectively prove that at the priority date of this patent, the corresponding problem still constituted a long-unsolved technical problem, nor could it prove that the technical solution of Claim 1 of this patent was the first to solve this technical problem. Furthermore, Merck could not effectively prove the correspondence between the Euthyrox product and the technical solution of Claim 1 of this patent, and the protection scope of Claim 1 was broader than the Euthyrox product. Therefore, the technical effects of the Euthyrox product could not be used to explain the technical effects of Claim 1 of this patent. The embodiments in the specification of this patent did not involve the technical effects brought by the distinguishing features between this patent and Reference 1, nor was there any acceptable evidence on record that could prove this patent achieved unexpected technical effects.
Ultimately, the Supreme People's Court of China determined that the challenged decision's finding that Claim 1 of this patent lacked inventive step was not improper. The appeal was dismissed and the original judgment was upheld.
Sunshine IP
From initially representing the client in filing the invalidation request with the China National Intellectual Property Administration to actively responding to the litigation as the third party in the first-instance and second-instance proceedings, Sunshine IP's professional team consistently stood on the challenging side, providing solid legal and technical support for the ultimate victory in this case.
The success of this case not only removed a potential patent obstacle for the research, development and production of related domestic drugs, but also once again demonstrated the important role of China's patent system in balancing patentee interests with social public interests and encouraging genuine innovation. At the same time, it sent a clear signal to all market participants: only technical solutions that truly possess inventive step can obtain stable protection under patent law.
As one of China's leading intellectual property service organizations, Sunshine IP has long been committed to providing high-quality, comprehensive intellectual property legal services to domestic and international clients. In this case, Sunshine IP's representatives, through their deep understanding of prior art in the chemical and pharmaceutical fields, precise grasp of patent law and examination standards, and extensive litigation experience, successfully identified key evidence from numerous prior art documents and clearly and forcefully expounded the reasons why the patent in question lacked inventive step, ultimately winning consistent recognition from administrative agencies to the highest judicial authorities. This is not only a victory for the client but also another demonstration of Sunshine IP's professional capabilities, and a powerful testament to the continuous optimization of China's intellectual property protection environment. Sunshine IP will continue to uphold its service philosophy of professionalism, rigor, and efficiency, contributing to stimulating innovation and maintaining a fair and orderly competitive market.
