Hua Xun IP Invalidation Case-Rivaroxaban I Composition Patent Declared All Invalid

2023Year10Month08State Intellectual Property OfficeDocument (Document No:2023092700362800)No.563806Review decision on request for invalidation, declaration200780049146.3No. of the invention.(hereinafter referred to"Involved Patent") All patent rights are invalid.The patents involved in this invalid case, the facts of the case and the information of the parties are shown in the following table:

【Legal basis for judgment]]

Patent Law No.22Article3Creativity under paragraph.

Key Points of Decision]

The identification of the technical problems actually solved by the invention is not necessarily directly equivalent to the technical problems that can be solved by the assertion claim of the specification, but should often be combined with the content of the embodiment and the existing technical content to make a comprehensive judgment. The technical effect of the invention relative to the closest prior art is the basis for determining the fact that the invention actually solves the technical problem, and the technical effect of the invention in the field of medicine is often confirmed by the experimental data recorded in the specification, and the degree of confirmation should be sufficient for those skilled in the art to determine. When the experimental data recorded in the specification is ambiguous and cannot prove that the invention has achieved the claimed technical effect, the claimed technical effect cannot be used as the basis for determining that the invention actually solves the technical problem and the creative invention.

【Reason and conclusion of invalid decision]]

1. The right of approval of the collegiate group1The main reason for not being creative

Right1The content:1.compositions, includingA)of the following formula5-Chlorine-N-({(5S)-2-oxo-3-[4-(3-oxo-4-Morpholino)Phenyl]-1,3-oxazolidine-5-Base}Methyl)-2-thiophenecarboxamide, (also known as "rivaroxaban");B)Acetylsalicylic acid (also known"Aspirin")andC)Clopidogrel.

Right1and evidence1The difference:Evidence1“CN1523986A"(see Instruction No.2Page16-18Line, No.18Page8-10Line) to the resource-to-community system.It includesA)Type(I)of oxazolidinones (can be rivaroxaban)B)Other active compounds, in particular with platelet aggregation inhibitors, anticoagulants, fibrinolytic agents, lipid-lowering agents, coronary therapeutic agents and/or vasodilator combination system) and its medical use.Right1and evidence1The other active compounds in combination with rivaroxaban are clearly defined as acetylsalicylic acid and clopidogrel.

Based on the above distinction1Technical problems actually solved: AlthoughInvolved Patent Specification No.0007,0198,0218-0239,0235,0239Contents recorded in paragraphOn the surface, it shows that:Right1The composition of the record has a synergistic effect, making it more than the individual active ingredients, formula.(I)Of oxazolidinonesAcetylsalicylic acid (orADPreceptor antagonists)combination, or acetylsalicylic acid andADPCombinations of receptor antagonists are more suitable for prevention and/or treatment of thromboembolic disorders, producing a significant increase in the performance of the antithrombotic effect of the platelet aggregation inhibitor in a thrombosis model.And essentially, first of all,Involved Patent Specification Table1and table2The experimental results are obtainedpvalues are compared, but the instructions do not clearly explain how to calculatepvalue, which prevents those skilled in the art from accurately judgingpThe value can reflect the exact technical effect of. And according to the table1experimental results, when1mg/kgAcetylsalicylic acid and3mg/kgWhen clopidogrel is combined, the results of its two measurements are converted.pvalues and experimental resultsshow that the same drug combination produces different technical effects.Same thing, the patentee in replyOA2In the supplementary experimental data submitted at the time, the table.1The results show the same1mg/kgProduced after clopidogrel administrationpThe value difference is large for different thrombus weight reduction effects, and the same difference also occurs in acetylsalicylic acid.+Clopidogrel group. After administration of the same drug composition, a large difference is obtained.pvalue, causing those skilled in the art to question the patent specification form in question.1and table2The reproducibility of the data and the above-mentioned supplementary experimental data and whether it is suitable for proving the technical effect of the patent in question.Secondly,AccordingpThe usual definition of the value,pValue refers to the probability that the statistical summary is the same as the actual observation data, or even greater, in a probability model, which is not a standard parameter model that reflects the synergy between substances. In the patent specification table involved1and table2in,pThe value reflects the level of difference in antithrombotic formation in the dosing group relative to the control group, not rivaroxaban.+Clopidogrel+Acetylsalicylic acid antithrombotic versus rivaroxaban or clopidogrel+Acetyl salicylic acidpvalue, does not reflect the rivaroxaban+Clopidogrel+Acetylsalicylic acid antithrombotic versus rivaroxaban or clopidogrel+Acetylsalicylic acid produces synergy. In addition, the patentee in replyOA2In the supplementary experimental data submitted at the time,AGroup data reflect clopidogrel, reserve+Clopidogrel has a very good anti-thrombotic effect,BGroup data reflection+Acetylsalicylic acid also has a good antithrombotic effect, which does not explain rivaroxaban+Clopidogrel+The combination of acetylsalicylic acid produces a synergistic effect. Therefore,Involved Patent Specification Table1and table2Only rivaroxaban can be sene+Clopidogrel+Acetylsalicylic acid is better than rivaroxaban or clopidogrel alone for antithrombotic effects+acetylsalicylic acid, this effect may only be the addition of the three.Above all, right.1relative to the evidence1The technical problem to be practically solved is to provide a drug combination of rivaroxaban with a better antithrombotic effect.

Technical implications:Evidence1Instruction No.24Page Table2Based on the disclosure that the combination of rivaroxaban and clopidogrel has a better therapeutic effect than either alone, those skilled in the art are motivated to combine rivaroxaban with clopidogrel.Evidence1(See Instruction No.24Page Table2)and/orEvidence3“Manolis S. Antonis, Tzeis Stylianos, Andrikopoulos George, Koulouris Spyros and Melita Helen, Aspirin and Clopidogrel: A Sweeping Combination in Cardiology, Current Medicinal Chemistry-Cardiovascular &Hematological Agents 2005; 3(3),and part of the Chinese translation'"No.20Page9-12Line and No.211Page Right Column2paragraph)The recorded content shows that although acetylsalicylic acid and clopidogrel belong to the same platelet inhibitors, their pathways of action are not the same, and the combined use of the two drugs has a stronger effect than that of the drug alone, while the side effects of bleeding complications are not excessively increased;Therefore, in order to improve the anti-thrombotic effect, the skilled person in the art is motivated to further add acetylsalicylic acid to the combination of rivaroxaban and clopidogrel, thus gaining the right.1The technical scheme.

2. The right of approval of the collegiate group2-5There is no main reason for creativity.

Right2-5The content:2.For preparation rights1The method of the composition is characterized.5-Chlorine-N-({(5S)-2-oxo-3-[4-(3-oxo-4-Morpholino)Phenyl]-1,3-oxazolidine-5-Base}Methyl)-2-Thiophene carboxamide, acetylsalicylic acid and clopidogrel are combined or prepared in a suitable manner.

3.Right1The composition is used for prevention and./or treatment of the condition.4.Drugs, including the right1The composition and, if desired, other pharmaceutically active ingredients.5.Drugs, including the right1The composition and one or more pharmacologically acceptable additives and./or carrier.

Right2-5The additional technical features cannot bring creative reasons:Relative to the right1The composition, right.2-5Neither the subject matter nor the additional technical features that are further qualified separately can bring about the intended technical effect;1The same reason for the comment, combined with the skilled person in the art in order to achieve the right.2-5The additional technical features corresponding to the conventional technical effects, motivated in the known right.1The composition is obtained on the basis of the right.2-5Additional technical features, and do not require creative labor.

3. The right of approval of the collegiate group6and right7There is no main reason for creativity.

Right6-7The content:6.Right1The composition is used for the preparation of prevention and./Or use of a medicament for treating a thromboembolic disorder.7.Right1The composition is used for the preparation of prevention and./or treatmentSTSegment elevation and noSTUse of the medicament for segment elevation myocardial infarction, stable angina, unstable angina, reinfarction and restenosis after coronary intervention, peripheral arterial occlusive conditions, pulmonary embolism, deep vein embolism and renal vein embolism, transient ischemic attack and thromboembolic and thromboembolic stroke.

Right6-7The additional technical features cannot bring creative reasons:Evidence1Instruction No.18Page11-14LineThe content of the record gives the technical enlightenment of the combination system composition for the treatment of thromboembolic disease, on the basis of which the skilled person in the art is motivated to put the evidence.1The combination of the disclosed drugs is also used for the prevention and treatment of thromboembolic diseases, thus obtaining the right.6technical solutions. by right6The review shows that the evidence1has been given the right1The composition is used for the revelation of thromboembolic diseases, and according to the patent specification in question, the right.7The defined diseases are all diseases related to thromboembolic disorders, and it cannot be concluded that the composition has achieved any unexpected technical effect on the treatment of these diseases; therefore, in order to expand the scope of application of drugs, those skilled in the art have the motivation to use the obtained pharmaceutical composition for the treatment of these diseases, and can obtain the right by verifying its technical effect through regular experiments in the art.7The technical program.

4. Conclusion

The right of the patent involved1-7It is not creative and does not comply with Patent Law No.22Article3The provisions of the paragraph shall be null and void.

【Right.Sharing of Understanding of "Invalid Program"]]

The idea of patent law is to encourage the public to become public prosecutors to actively invalidate improperly authorized patents in order to compensate for the lack of the patent office's ability to examine them and to appropriately limit the shortcomings of patent monopoly. On the one hand, Nanjing Huaxun's active invalidation of intellectual property rights is to promote the development of the domestic generic drug industry, on the other hand, it is also in response to the requirements of the patent law to break patents that should not be authorized, so that the technology can be shared with the public earlier.