[Top Ten 2022 Cases] Patent Invalidation Cases Related to Antidepressant Voltioxetine

Patentee:H· Lundbeck Ltd.

Requestor: Chengdu Kanghong Pharmaceutical Group Co., Ltd.

Patent name: Phenylpiperazine derivatives as serotonin reuptake inhibitors

Patent Application No:02819025.4

case background]

The drug Vortioxetine involved in this case is one of the most expensive antidepressants currently available, as2022years have been globally95The listing license in the country and region.2022Global sales in more42billion yuan. This case is a patent challenge initiated by a generic drug applicant against the original drug. The case mainly involves legal issues such as insufficient disclosure. After hearing, No.54793The invalidation request examines the decision to maintain the validity of the patent right.

Key Points of Decision]

The medical use required for full disclosure of a pharmaceutical compound should not be construed narrowly as a use at the level of an indication. If there is a consensus in the art on the relationship between the mechanism of action and the ultimate indication, and based on the validation of the mechanism of the drug compound, it is reasonable to anticipate the likelihood that it will eventually be used as a drug for an indication, the specification shall be deemed to satisfy the patent law for the use of chemical products and/or use effect disclosure requirements.

【focus of controversy1]]

What are the technical problems to be solved by the patent involved?

The claimant's point of view: the patent in question claims to solve the technical problem of providing a class of serotonin ((5-Serotonin,5-HT)) reuptake inhibition and5-HT_2CNovel compounds with dual mechanisms of receptor antagonism for the effective treatment of affective disorders, including depression, anxiety and obsessive-compulsive disorder, the specification does not give specific experimental data indicating the claims.1-7The compounds are compounds of dual mechanism of action. Therefore, there is a defect of insufficient disclosure, which is not in accordance with the patent law.26Article3paragraph.

Views of the collegial panel:When it is claimed in the specification that the invention can solve technical problems at multiple levels, in principle, as long as those skilled in the art can determine that one of the technical problems at one level is solved, the requirements for full disclosure of the specification are met.. In this case, in the case where the skilled person in the art can determine that the invention can solve the technical problem of serotonin reuptake inhibition (the first level of technical problems), regardless of whether the instructions verify that the compound can have both.5HT_2CReceptor modulation (second-level technical problem) is not a reason to consider that the specification is not sufficiently disclosed.

In summary, the technical problem to be solved by the patent in question should be determined to provide as a serotonin reuptake inhibitor.(SSRIs)The collegial panel did not support the determination that the patent involved should solve the technical problem of "dual mechanism.

【focus of controversy2]]

In combination with the prior art and the test results of the patent specification in question, those skilled in the art can reasonably expect that the compound of the patent in question has the possibility of being used for antidepressant treatment.

(1) on the relationship between serotonin reuptake inhibitors and antidepressants

Requester's view: The mechanism of depression is complex, the mechanism between the effect of serotonin reuptake and the successful treatment of depression is not clear, and so-called serotonin reuptake inhibitors do not exist in the prior art.

The view of the collegial group: combined with the evidence,Serotonin is one of several neurotransmitters that are closely related to depression, and inhibition of serotonin reuptake is a very important channel for anti-depressant treatment. Despite the existence of antidepressant drugs known in the prior art"Selective5-Serotonin reuptake inhibitorThis category, and5-Selective antidepressant activity of serotonin is important. But that doesn't mean only reaching"Selective5-Serotonin reuptake inhibitorOnly by the standard can the compound eventually be used as an antidepressant treatment. Based on the understanding of the existing technology as a whole for antidepressants, the skilled person in the art can expect that compounds with serotonin reuptake inhibition can be used as-.Potential compounds for antidepressants, this expectation is not altered by the classification of marketed antidepressants in the prior art.

(2) The relationship between in vitro experiments and treatment of depression

Requester's opinion: The technical effect of the compound should be determined and considered according to the indication. The results of the in vitro serotonin uptake inhibition assay in rats given in the specification do not directly correspond to the presence or absence of antidepressant activity. Therefore, there is a defect of insufficient disclosure, which is not in accordance with the patent law.26Article3paragraph.

Views of the collegial panel:First of all, the patent law, implementing regulations and patent examination guidelines do not explicitly stipulate that the technical problems or effects of drug compounds must rely on the verification of specific indications.It is true that the medical use of a compound that can be directly used for a specific indication is more suitable for the compound to be directly manufactured or used in the industry, but this does not mean that the verification of the medical use must go to the level of the indication. On the one hand, the standard of patent law to protect inventions and creations is different from drug marketing approval. Considering from the original intention of patent law legislation, if the technical personnel in this field can predict the use of the drug compound involved in medicine according to the relationship between indication and mechanism of action, even if the verification of medical use is not directly applied to the treatment of a certain indication of human body, the protection of such drug compounds is in line with the legislative purpose of encouraging invention and creation and promoting scientific and technological progress. On the other hand, if there is a consensus in the field on the relationship between the mechanism of action and the final indication, and by verifying the mechanism of action of the compound, those skilled in the art can reasonably expect that it has the possibility of being eventually applied to a drug for the treatment of a certain indication, it should be considered that it meets the requirements for the use of chemical products in the patent law./or use effect disclosure requirements.Secondly, the in vitro test has its unique significance.The screening of drug compounds usually requires multiple steps. Preliminary in vitro tests can narrow the scope of screening compounds and provide a basis for subsequent research, the high cost of clinical trials and ethical factors make it impossible to replace in vitro tests or animal in vivo tests. Due to the different test objects, some of the compounds with activity in vitro tests may not be considered to have the prospect of drug development in vivo tests, but this does not completely deny the significance of in vitro experiments. Specifically in this case, the prior art has clearly taught the relationship between serotonin reuptake inhibitory activity and antidepressants, and in this case, the possibility of demonstrating the antidepressant effect of the compound is fully understood by those skilled in the art by verifying the serotonin reuptake inhibitory activity of the compound through in vitro experiments, the relationship between serotonin reuptake activity and anti-depression does not have to be undisputed to the extent claimed by the claimant in order to recognize the research value of the experiment. The effect that can be confirmed based on the results of in vitro tests shall also be regarded as the technical effect of the technical scheme in the sense of patent law.

to sum up,A person skilled in the art can anticipate the prospects of the compounds of the patent in question in the field of antidepressants based on the results of in vitro experiments.

【Revelation]]

The drug development cycle is long, and the timing of compound patent applications is critical to the protection of drug innovation. The examination of the full disclosure of such applications should not only avoid the protection of inventions that do not belong to the meaning of the patent law and technical solutions that have not been actually completed, thus eroding the interests of the public, but also avoid the use of the existing technology from the overall status of the existing technology./The verification of the use effect is too high, which damages the interests of the patent applicant and the enthusiasm for innovation.