Ruxolitinib, a selective JAK1/JAK2 inhibitor developed by Incyte Corporation, works by blocking the JAK-STAT signalling pathway, which is closely associated with the pathogenesis of various inflammatory diseases and myeloproliferative neoplasms (MPNs). Ruxolitinib was first approved for marketing in the United States in November 2011, for treating intermediate- to high-risk myelofibrosis (MF), and subsequently approved in the United States for treating hydroxyurea-resistant/intolerant polycythaemia vera (PV) (in December 2014), steroid-refractory acute graft-versus-host disease (GVHD) in patients aged 12 years and older (in May 2019), steroid-refractory chronic GVHD (in September 2021), atopic dermatitis (Opzelura", 1.5% cream, the first topical JAK inhibitor, in December 2021). In March 2017, Ruxolitinib was launched in China for treating intermediate- to high-risk MF.
The patentee has established a sophisticated and comprehensive patent portfolio strategy across the United States and key global jurisdictions. This ranges from, for example, foundational compound patents (e.g., US 7,598,257), to crystal and formulation patents (e.g., US 8,729,094), and further to indication patents (such as the GVHD-directed patents (e.g., US 9,993,467) and the atopic dermatitis-directed patents (e.g., US 10,925,753). Additionally, the patentee has secured protection for synthesis methods (e.g., US 8,722,693) and combination therapies (e.g., with PD-1 inhibitors).
Due to the significant economic benefits of this drug, many challenges have been made by multiple pharmaceutical companies in China against this patent portfolio, including the request for invalidation against the invention patent entitled "salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl)-3-cyclopentylpropanenitrile (CN Patent No.: ZL200880102903.3)", filed by the petitioner Chongqing Pharscin Pharmaceutical Co., Ltd. on 8 February 2024.
For this invalidation case, after examination, the CNIPA eventually issued Decision No. 580173 on the Request for Invalidation on 30 August 2024, maintaining the validity of the patent based on the granted text.
As can been seen from the Decision, this invalidation case primarily focuses on the following two aspects: (1) Can the disclosure in the cited document(s) constitute part of the application document? (2) To what extent shall the priority document disclose so that a subsequent application is entitled to priority?
(1) Can the disclosure in the cited document(s) constitute part of the application document?
The petitioner holds that the cited document was published later than the priority date of the patent at issue, and thus its disclosure cannot constitute part of the disclosure of the patent at issue.
The patent at issue was filed on June 12, 2008, with a priority date of June 13, 2007. The patent at issue cites in the Background section the US patent application No.11/637,545 filed on December 12, 2006 (hereinafter referred to as "the cited document"), which discloses several JAK inhibitors including Ruxolitinib. However, the cited document was published on June 14, 2007, one day later than the priority date (June 13, 2007) of the patent at issue.
Since the patent at issue was filed on June 12, 2008, this case should be subjected to the Chinese Patent Law amended in 2000 and implemented in 2001, and the Implementing Regulations of the Chinese Patent Law amended in 2002 and implemented in 2003.
The "Guidelines for Patent Examination(2006)" stipulates in Part II, Chapter 2, Section 2.2.3: "the cited document(s) shall also meet the following requirements: ... (2) The cited non-patent document(s) and foreign patent document(s) shall be published prior to the filing date of the application; the cited Chinese patent document(s) shall be published no later than the publication date of the application."
According to this stipulation, the disclosure in the cited document cited in the Background section of the patent at issue shall not constitute part of the disclosure of the patent at issue.
However, in the latest Guidelines for Patent Examination (2023), the above stipulation has been revised to read: "... (2) The cited non-patent document(s) shall be published prior to the filing date of this application; and the cited patent document(s) shall be published no later than the publication date of this application."
It can be seen that the Guidelines for Patent Examination (2023) have liberalized the restrictions on the publication date of the cited foreign patent document(s), possibly for the following reasons: Firstly, when addressing transitions between the old and new versions of the Guidelines for Patent Examination, the legislative principle of "retroactive application with favourable provisions" should be followed. Secondly, the new stipulation provides applicant(s) greater flexibility to cite document(s) that more accurately reflect the technical background in the Background section, facilitates the understanding, search, and examination of the invention or utility model, and also aligns the examination standards at the national phase of PCT international application(s) with those at the international phase, thereby avoiding unnecessary examination disputes. Thirdly, the new stipulation is more conducive to implementing the priority system, is beneficial for the protection of inventions and creations, and aligns with the legislative intent of the Chinese Patent Law.
In view of the above, for this case, the collegial panel ultimately adopted the new stipulation of the Guidelines for Patent Examination (2023). That is to say, the collegial panel holds that the disclosure in the cited document constitutes part of the disclosure of the patent at issue.
(2) To what extent shall the priority document disclose so that a subsequent application is entitled to priority?
The petitioner holds that the disclosure in the cited document cannot constitute part of the disclosure of the patent at issue, and neither the priority document nor the prior art discloses any experiment for efficacy validation or efficacy data on the salt of Ruxolitinib, and thus the patent at issue is not entitled to priority.
The ChinesePatent Law provides in Article 29, Paragraph 1 that: "if an applicant, within twelve months from the date on which the applicant first filed in a foreign country an earlier patent application for invention or utility model, or within six months from the date on which the applicant first filed in a foreign country an earlier patent application for design, files in China a subsequent patent application for the same subject matter, the subsequent application is entitled to priority in accordance with any agreement concluded between the said foreign country and China, or in accordance with any international treaty to which both countries are party, or on the basis of the principle of mutual recognition of the right of priority."
Regarding the same subject matter, the Guidelines for Patent Examination (2023) stipulate that "the inventions or utility models sharing the same subject matter as referred to in Article 29 of the Chinese Patent Law means inventions or utility models that are identical in terms of the technical field, technical problems to be solved, technical solutions, and expected effects." And in the field of pharmaceutical chemistry, due to the high unpredictability of technical effects, it is generally necessary to include qualitative or quantitative experimental data in the specification sufficient to prove the achievement of the intended use and/or the expected effects, so that those skilled in the art can be convinced that the invention can achieve the intended use or effect. Accordingly, in the evaluation of 'the same subject matter' in this field, there is a high degree of reliance on experimental data when determining whether the earlier and subsequent applications have the same technical effects.
As far as this case is concerned, firstly, as mentioned above, the disclosure in the cited document can constitute part of the disclosure of the patent at issue. The cited document has disclosed the preparation methods for Ruxolitinib and its enantiomer, as well as their trifluoroacetate salts, and has disclosed that it was discovered in JAK inhibitory activity assays that both trifluoroacetate salts exhibit activity, with one enantiomer showing higher activity than the other.
Secondly, those skilled in the art know that "salt formation generally does not cause the loss of activity of a drug compound." Therefore, as the cited document has disclosed that the trifluoroacetate salt of Ruxolitinib possesses JAK inhibitory activity, those skilled in the art would understand that Ruxolitinib itself also possesses JAK inhibitory activity.
On such basis, those skilled in the art can directly and unambiguously conclude that Ruxolitinib possesses JAK inhibitory activity.
In conclusion, the priority document of the patent at issue and the patent at issue itself indirectly disclose through the cited document that Ruxolitinib possesses JAK inhibitory activity. Therefore, the patent at issue is entitled to priority.
Insights and Considerations
Firstly, when drafting the patent application document by citing other document(s), one shall carefully consider whether the content in the cited document(s) can constitute part of the specification of a patent application.
On the one hand, the requirements for the publication date of the cited document(s) vary depending on the type of the cited document(s). When a non-patent document is cited, it should be published prior to the filing date or priority date (if any) of the patent (application); while a patent document (including the Chinese patent document and the foreign patent document) is cited, it should be published no later than the filing date or priority date (if any) of the patent application. On the other hand, not all content of the cited document(s) can constitute part of the specification of the patent (application), and only when the patent (application) explicitly refers to the content of the cited document(s), such content can constitute part of the specification of the patent (application).
Thus, to be on the safe side, for the content which is essential to implement the invention, it is advisable to make disclosure in the application document in an explicit manner rather than by citing other document(s).
Secondly, the extent of disclosure in an earlier application relative to a subsequent application determines whether the subsequent application is entitled to priority. Whether the subsequent application is entitled to priority depends on whether the technical field, technical problem, technical solution, and expected technical effects disclosed in the two documents are the same. And for the applications in the field of pharmaceutical chemistry, due to the high unpredictability of technical effects, it is necessary to include qualitative or quantitative experimental data in the specification of the priority document sufficient to prove the achievement of the intended use and/or the expected effect, so that those skilled in the art can be convinced that the invention can achieve the intended use or effect; otherwise, the subsequent application may fail to claim priority. Nevertheless, the subsequent application may further include experimental data not contained in the earlier application, but such experimental data can only serve as supplementary evidence and cannot independently support priority entitlement.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.
