A Stratification Too Far? How the CNIPA Draws the Line on Patient Subgroups in a Recent Precision Medicine Invalidation Case

Precision medicine is rapidly transforming the global healthcare landscape, providing more effective therapies and better patient outcomes through targeted solutions. As therapeutics move away from the traditional “one-size-fits-all” model, unique challenges are presented in the patent examination process.

The 2024 Top 10 Patent Re-examination and Invalidation case highlighted below provides further insight into how the China National Intellectual Property Administration (CNIPA) interprets claim scope and inventive step during the examination of precision medicine technologies.

Background

Generic Drug maker Chia Tai Tianqing Pharmaceutical Group filed an invalidation request before the Patent Re-examination Board (the “Board”) against an invention patent titled “Use of Degarelix¹ in the Preparation of a Medicament for Treating Metastatic Prostate Cancer“², owned by Ferring International Pharma (Switzerland), on the basis of lack of inventiveness.

Claim 1 of the captioned application recites the following:

Use of Degarelix in the preparation of a medicament for treating metastatic prostate cancer in a subject, wherein the treatment comprises:

• administering an initial dose of Degarelix in an amount of 160 to 320 mg; and
• subsequently administering a maintenance dose of 60 to 160 mg once every 20 to 36 days,

wherein the subject has a pre-treatment baseline serum alkaline phosphatase level (sALP) of approximately 150 IU/L or higher.

The closest prior art was a clinical trial publication which disclosed most features of the claim, with the exception of the pre-treatment sALP level subject requirement.

The core argument centered on how to interpret the claim scope of the precision medicine invention, specifically how claim limitations are read. The Board assessed whether such a physiological biomarker – though related to disease progression – was significant enough to be considered a valid limitation in order to support inventive step. Ultimately, the CNIPA invalidated the patent, offering important guidance on claim interpretation and inventive step in the context of precision medicine.

Understanding Scope of the Claims

Under Article 25 of the Chinese patent law, methods of treatment are not patent eligible subject matter. Treatment methods can only be protected as Swiss-type claims, which are normally read as “use of x for the manufacture of a medicament for treating y”. Typically, there are three types of features which are considered limiting in this type of claim:

• X – the active ingredient, for example, a small molecule;
• Y – a medical indication, for example, a cancer subtype;
• Manufacturing process³ (not applicable in the present case).

In this case, the Examiner considered certain additional features of claim 1, (e.g., the initial dosage, maintenance dosage, and frequency of dosing) to relate solely to treatment administration (which are only involved after the manufacturing process, e.g., per the doctor’s instructions). Therefore, the CNIPA did not consider these features as being limiting to the manufacturing process, and thus not considered valid limitation to the claim scope.

Examining Inventiveness

Excluding the non-limiting features of claim 1, the Board analyzed the remaining features in the claim:

• Active ingredient – Degarelix
• Disease indication – metastatic prostate cancer
• Specific physiological parameter – subjects having pre-treatment baseline sALP level of 150 IU/L or above

The closest prior art presented⁴ at the invalidation proceeding was a published phase III clinical trial study using Degarelix in prostate cancer patients. The study disclosed a 97.2% positive treatment response rate across patients of various disease stages, of which 20% were metastatic prostate cancer patients.

The only differentiating feature of the claimed invention from the prior art was the pre-treatment baseline sALP level range in the indicated patient group (the patentee also indicated it should be understood as a novel disease sub-type in the claim during the invalidation procedure).

Determining Technical Problem Solved

In order to evaluate inventive step, the CNIPA needs to determine a) the technical problem solved by the differentiating feature and b) determine whether the prior art as a whole provides motivation to solve the problem through structural modification.

Was the pre-treatment baseline sALP level a valid claim limitation that affected the technical problem that was solved? A feature can be considered “limiting” if it contributes to a specific technical effect over the prior art. In this case, for example, limitations to the treatment of a specific patient subgroup may be acceptable if the treatment is directly linked to a differentiating technical effect in that patient subgroup.

The patentee argued that the limitation of metastatic prostate cancer in combination with pre-treatment baseline sALP level range resulted in a specific target patient group having a disease subtype not described in the prior art, namely prostate cancer patients with bone metastasis.

While the Board acknowledged that the specification demonstrated that “sALP reduction in the selected patient group was more effective than in patients with other disease stages”, they reiterated there is no evidence that persons having ordinary skill in the art (PHOSITAs) agreed that pre-treatment sALP levels alone could be used to classify a new prostate cancer subtype.⁵ As a result, the Board concluded that the technical problem solved was limited solely to the use of Degarelix in treating patients with metastatic prostate cancer.

Determining Technical Effect of the invention

Despite the fact that the applicant had shown effective sALP reduction in certain subjects in the specification, the Board emphasized that the applicant needed to provide evidence supporting that sALP level changes over time can act as a single marker to measure disease progression and treatment outcome. The Board stated that the patentee’s data was merely “an analysis of physiological parameter changes during treatment of patients with specific pre-treatment baseline sALP level”. Without a clear link to a specific technical effect, these types of changes would not rise to the level of being a valid limitation in a Swiss-style claim.

As no new disease indication or corresponding treatment effect (against prostate cancer) was identified, the Board invalidated the patent on the grounds that inventiveness cannot be determined without these elements.

EIP Thoughts

So what is the standard for protecting certain patient sub-groups?

When protecting precision medicine technologies, it is common to add limitations to certain features that identify patient sub-groups within a broader disease indication.

The present decision emphasizes that the Board looks for “clinical guidance value” in these claimed features when determining whether to consider such “disease marker” type limitations. Specifically, the Board looks at inventiveness – whether a PHOSITA would think that the feature (combined with the knowledge in the art) is valuable in guiding clinical decisions.

In the present case, the limiting disease marker, sALP level alone, was not definitive on its own to identify a new and meaningful patient group. In fact, sALP also correlates to other physiological outcomes. For example, even healthy individuals or individuals with other diseases can have the same elevated levels of sALP.

A disease marker needs to be clear, significant and definitive for PHOSITAs, as these markers are only meaningful if they can accurately stratify patients, enabling subsequent treatment to be assigned appropriately.

We believe that a crucial step to protecting these features is to present a clear relationship and connection between the limiting disease marker, the disease indication, and subsequent treatment outcomes in the specification. In this example, if the patentee had provided evidence showing that only patients having sALP levels at 150 IU/L or above responded surprisingly well to the treatment, then the Board may have recognized the sALP level as a limiting feature in the claim because a patient’s sALP levels would guide the clinical decision of a doctor. The claim(s) would likely be considered inventiveness based on the surprising technical effect.

What is “agreed” in the art?

While we now understand the importance of linking disease markers with how they guide clinical decisions, how can we determine what is “agreed upon” between PHOSITAs? When is a particular mutation or sub-population considered a new disease?

In an article published by members of the Board in charge of this case⁶, the authors provided further discussion into this issue of classifying diseases.

Specifically, they pointed out that there are a number of disease classification systems (whether it be international systems, such as the International Classification of Diseases (ICD), national systems, or systems categorized by academic associations under specific disciplines), that may not be compatible with each other. At the same time, it is almost certain that technological and clinical advances will evolve faster than the systems themselves, as these classification systems go through meticulous and long processes in producing updates. For example, while HER2-positive breast cancer has been classified clinically and treated with targeted therapy for decades, it was only just recently added in the FY 2025 ICD update^7[7].

The article confirmed that the standard for claiming new patient subgroups or disease classifying markers is not based on whether a disease is listed in well-established systems (e.g., covered in the ICD). Instead, patent examiners will use a more flexible approach, taking into account other factors to determine what is considered a clinically recognized disease.

As suggested by the Board’s comments, as long as a claimed disease marker carries substantial “clinical guidance value”, we believe having sufficient clinical data demonstrating such guidance value can support limiting a disease to a new patient subgroup. However, it is still unclear if earlier stage data, such as using only pre-clinical data, would be sufficient to support a new subgroup.

This case highlights the ever-present tension that clinical stage companies face between the (earlier) public disclosures of clinical trial information with the ultimate confirmed results of the clinical trial. Prior published clinical trial information (required by the US FDA) typically discloses the medicament, the disease to be treated, and expected outcomes. Because China’s patent laws do not allow method of treatment claims (thus excluding dosing schedules, dosing regimens, and other types of new IP that could arise from a clinical trial), clinical stage companies have more limited options when it comes to protecting IP in China at this later stage of a product’s development. Finding strong relationships between various disease markers and disease outcomes is a solid way to obtain additional IP protection from clinical trial results in China.

This article is for general informational purposes only and should not be considered legal advice or a legal opinion on a specific set of facts.

1. Degarelix is a GnRH antagonist that lowers testosterone levels in the body.

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2. Patent No. ZL200980104713.X

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3. Features such as physical characteristics of the manufactured product or routes of administration may be considered as valid limitations that limit part of the manufacturing process. However, whether the CNIPA will accept these limitations is based on if these features substantially affect the claimed manufacturing process. For example, one of skill in the art would expect a different manufacturing process for an oral formulation and a subcutaneous injection carrying the same active compound. However, if in fact the manufacturing process is the same, even with a different delivery method (e.g. same formulation injected at different locations with known routine modified process), the CNIPA will likely not consider such different routes of administration as limiting.

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4. Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, Jensen JK, Olesen TK, Schröder FH. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008 Dec;102(11):1531-8. doi: 10.1111/j.1464-410X.2008.08183.x. PMID: 19035858.

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5. Changes in bone turnover and osteoblastic activity, caused by cancer bone metastasis, may be reflected in ALP level changes. Although the priority date of this patent is in 2009, even at least up to 2023, serum ALP levels was still not a well-recognised marker for prostate cancer bone metastasis due to its correlation to several non-neoplastic illnesses, low diagnostic sensitivity and lack of well accepted cut-off value used across different researchers. See more at: Biomarkers for Prostate Cancer Bone Metastasis Detection and Prediction

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6. https://www.cnipa.gov.cn/art/2025/6/6/art_2648_200011.html

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7. https://libmaneducation.com/icd-10-cm-for-2025-new-codes-for-hormone-status-in-breast-cancer/

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