Case study on examination criteria of pharmaceutical purpose claims - from the Gleevec patent invalidation case

Gleevec, which was only known to the medical circle and the patient community, catapulted into the public eye with the release of movie "Dying To Survive" and was highly debated.

"magic potion" Gleevec

Gleevec (Imadinib), whose active ingredient is imatinib mesylate, is a molecularly targeted drug for the tyrosine kinase BCR-ABLdeveloped by Novartis, and is also the first successfully developed small molecule targeted drug in history. It was first approved by the US Food and Drug Administration (FDA) for listing on May 10, 2001. Currently, the drug has been approved for listing in more than 110 countries. It pioneered the age of targeted therapy for tumor molecules, and was hailed as a landmark discovery. It was also listed as one of the world's top ten technological breakthroughs in 2001 together with human genetic engineering.

Gleevec is now a first-line drug for Philadelphia chromosome-positive chronic myeloid leukemia, for the treatment of patients with chronic myeloid leukemia (CML) blast crisis, accelerated phase, or chronic phase after failure of α-interferon therapy. Besides chronic myeloid leukemia, Gleevec has been developed for the new use of gastrointestinal stromal tumors (GIST). Patients who continue to take medication can also achieve long-term survival.

Background of the invalidation case

The patent for pharmaceutical compounds of Gleevec expired in May 2013. Jiangsu Hansoh Pharmaceutical's Imatinib mesylate generic drug Xinwei (Xin Wei) was approved for listing and clearly shared the market share of Gleevec. In order to curb Xinwei into the market, Novartis filed a lawsuit against the Beijing Second Intermediate People's Court, accusing the generic drug Xinwei of Hansoh infringed the rights of Novartis patentNo. CN1276754C. This patent protects Gleevec's second medical use for the treatment of gastrointestinal stromal tumors, and its original estimated expiration date is October 2021.

Subsequently, Hansoh launched a counterattack and filed a patent invalidation request with the Patent Reexamination Board of China National Intellectual Property Administration (CNIPA) on September 5, 2014. On October 23, 2015, the Patent Reexamination Board made a decision of the invalidation request. They considered that the patent-in-suit did not have inventiveness stipulated in Art. 22.3 of the PRC Patent Law, and declared that the patent was invalid.

Novartis then appealed to the Beijing Intellectual Property Court. The court rejected the appeal and maintain the decision of Patent Reexamination Board. Novartis refused to accept the judgment and appealed to the Beijing Higher People's Court. On December 20, 2017, the court rejected the appeal and upheld the original judgment.

Highlights of the invalidation decision

Claim 1 of the patent-in-suit is a pharmaceutical purpose claim. The pharmaceutical purpose claims is essentially special provisions for not granting patent rights to the treatment method of diseases in PRC patent law. Balancing the interests of the public and the rights holders by providing a necessary protection space and motivation system for medical purpose inventions. Such claims are generally written as " the use of compound X in the manufacture of a medicament for treating Y disease " or a form similar thereto. Which typically have three main features: compound X, drug prepared from compound X, and treating Y disease.

The Patent Reexamination Board made a clear guidelines on the pharmaceutical purpose claims, that is, in the pharmaceutical purpose claims written in the form of "the use of compound X in the manufacture of a medicament for treating Y disease", "treating Y disease" is understood to mean "effective for treating a patient suffering from the disease". It cannot be understood as "effective forIn vitrocell experiments on the disease" or "effective for animal models of the disease". Based on this, the Patent Reexamination Board provides a clear examination standard for the prior art disclosure level in the novelty evaluation of this type of claim.The medical use invention is novel if the content disclosed in the prior art does not reflect the exact conclusion that the compound can effectively treat the patient with the disease.

In the case of inventive judgement to analyze whether those skilled in the art will try to obtain the technical solution, the Patent Reexamination Board put forward the criteria for “reasonable success expectations”. When judging whether the invention is obvious relative to the prior art, it is not only necessary to consider whether those skilled in the art will try to use the compound to treat disease (Try the technical solution), but also whether the attempt has a reasonable success expectation (Reasonably foresee that the solution can solve the technical problems and achieve the expected effects).If those skilled in the art would consider trying to treat disease with the compound and has reasonable success expectation, then the invention of the medical use is not inventive. Wherein reasonable success expectations are not equivalent to absolute success expectations.

Beijing Higher People's Court decision

Regarding the issue of creativity, the court held that evidence 1 has taught that the trial of GIST with the selective tyrosine kinase inhibitor STI571 is a “new systemic treatment approach”. The early results of the test appear to be exciting, so those skilled in the art have an incentive to use STI571 to treat GIST, that is, the technical solution described in Patent Claim 1.

As for whether those skilled in the art has a successful expectation of STI571 to treat GIS, Novartis proposes a low success rate of anti-tumor drug development, and there is no successful precedent for single-drug targeted therapy for solid tumors in the prior art. However, the court held that this does not affect the conclusion that those skilled in the art can reasonably expect that ST1571 can effectively treat GIST. The inventive judgement only needs reasonable success expectations, and does not require absolute success expectations.

Novartis also believes that the patent-in-suit has achieved unexpected technical results. In this regard, the court held that the unexpected technical effect of the invention means that the technical effect produced a "quality" change compared with the prior art, with new performance or a change in "quantity". Such "quality" or "quantity" changes are unpredictable or inferred by those skilled in the art in advance. The technical solution described in the patent claim 1 does not produce new performance, and does not exceed the effect expected by those skilled in the art with respect to the evidence 1.

The court finally decided to reject the appeal and upheld the original judgment.

Conclusion

The novelty and inventive judgment of the pharmaceutical purpose claims, in particular the second pharmaceutical purpose claims, are very complex legal issues and have been widely controversial. Judgment difficulties include the interpretation of the scope of claims, what extent the comparison document is disclosed can be considered to disclose the invention, the standards of inventiveness, and how to determine the expected technical effects, etc..

After the decision was issued, causing widespread concern in the industry. The legal profession said that the verdicts of the Novartis v. Hansoh case has made exploratory analysis and judgment for the novelty and inventive examination of the second pharmaceutical purpose claims, and give clear and actionable opinions. This is conducive to the accurate understanding of patent examination standards by the industry and the public, and clearly form reasonable expectations, which has important guiding significance for similar issues in the field. It will have significant and far-reaching impact on patent protection strategies and business activities in China for global innovative pharmaceutical companies and generics companies.