The biggest enemy of patent registration lies in the inside...
It is important to control on the disclosure of information on efficacy and effect…
The brightest star in the pharmaceutical bio-industry is thought to be a new drug, especially a first-in-class drug. An innovative drug typically involves the development of new pharmaceutical uses of novel substances which have never been before, and there may be included a case that although the substances are previously known, pharmacological effects are shown for new indications other than existing indications.
The former can be granted a right as <Substance patent>. On the other hand, the latter may be linked to a case of expanding the range of indications of an already marketed matter or drug repositioning, which attempts to develop a substance, that has failed in development, for another indication.
We can find numerous cases when looking for drugs widely known in the market for <Indication expansion> or <Drug repositioning>. For example, Viagra (sildenafil) can be a representative case of drug repositioning as it was developed as a treatment for angina pectoris and became a global blockbuster through a side effect discovered incidentally. On the other hand, Finasteride, which has been successfully developed as a treatment for hair loss (Propecia) in addition to a treatment for prostatic hypertrophy (Proscar), is a case of indication expansion which everyone knows.
Enbrel (Etanercept), which has recently been controversial (whether it is actually controversial is another issue) as possible its therapeutic or preventive effect on Alzheimer's disease was hidden from the public, is also a case with sufficient possibility of expanding indications or drug repositioning.
Indication expansion or drug repositioning as described above is not to be belittled as a mere discovery of new indication in known substances, but rather is highly worth being protected as a patent in that it has discovered a new pharmaceutical use which could not have been predicted at all from previously known facts. However, in terms of patents, there is no real benefit in categorizing indication expansion or drug repositioning, and they can all be bundled together and granted a right under the name of <Use invention for pharmaceutical>.
From now on, issues which are problematic in practical business with respect to pharmaceutical use invention shall be reviewed.
"Use inventions for pharmaceutical have very strict description requirements for specification."
In KIPO practice, it is sufficient to describe the usefulness of the substance for a substance invention, and it is not required to describe the data confirming that each substance has a pharmacological effect.
However, a use invention for pharmaceutical is an invention for a new pharmaceutical use of a known substance, and whether or not there is a pharmacological effect on the pharmaceutical use itself is a requirement for the completion of invention. Therefore, in the nature of such use inventions for pharmaceutical, whether the pharmacological effect is confirmed is very important, and the experimental data confirming such effect is required to be described in the specification from the time of filing. The requirement to describe the experimental data on pharmacological effect is the same in the case of combined administration. It is difficult to predict whether a pharmacological effect will occur when administered in combination unless it is confirmed by an experiment, even among drugs with the same pharmacological mechanism. Therefore, experimental data on the pharmacological effect of combined administration should be described.
According to the judicial precedents, if the pharmacological mechanism is clearly identified, such experimental data can be exempted from being described. However, if the pharmacological mechanism for a specific indication has been identified, it can lead to the logic that the pharmacological effect is easily predicted, so there is a high possibility that the inventive step will be problematic. Therefore, it is a very risky approach to have a thought of not describing experimental data based on the fact that the pharmacological mechanism has been identified.
In addition, it may be desirable to broaden the scope of rights in the case of use inventions for pharmaceutical by describing the active ingredients in Markush format as in substance inventions. However, compounds without confirmation of pharmacological effects are in violation of description requirements due to insufficient experimental data on the pharmacological effect. Therefore, if intending to acquire a right related thereto in a wide range, it will be necessary to secure the experimental data for the desired range.
The reason why the description of experimental data in specification is emphasized in the use inventions for pharmaceutical is that there is no opportunity at all to supplement this after filing, unlike substance inventions. It is an established legal principle that if the experimental data is not described at the time of filing, the applicable scope is handled as an incomplete invention, and any attempt to supplement it later is deemed to be an attempt to complete the incomplete invention and is not permitted. Therefore, if intending to file for a use invention for pharmaceutical, it is most important to have the experimental data on pharmacological effects from the time of filing and prepare a specification scrupulously to ensure that the experimental subject and the experimental data are well matched.
"When is the most appropriate time to file for use inventions for pharmaceutical?"
In principle, clinical trial data should be submitted for experimental data on use inventions for pharmaceutical. However, it is mostly impossible in many cases to secure such data as product development should proceed up to a considerable degree in order to secure clinical trial data, and there are too many gates to go through, including IND. In the end, description of in-vitro or in-vivo data is allowed in the practical business of deliberation. If so, when is the most appropriate time to file among the dates when in-vitro data, in-vivo data, or clinical trial data are obtained?
Use inventions for pharmaceutical (mostly drug repositioning) of universities or public research institutes in Korea are mostly for the purpose of out-licensing while not being the principal body of commercialization, so inevitably, they are filed for application based on in-vitro or in-vivo results. However, because it is difficult to predict the probability of clinical success from such initial data, if the result is not very promising, there are demerits that it is difficult to exclude the possibility of not receiving any attention at all in the technology transfer market and of being stored away lying unused.
On the other hand, a pharmaceutical company preparing for direct commercialization can diversify its application strategy according to the contents of use invention for pharmaceutical.
For example, in the case of gastrointestinal stromal tumor (GIST), which is a new pharmaceutical use of Gleevec, a treatment for chronic myeloid leukemia (CML) (the Supreme Court hu502 decision rendered on Jan. 31, 2019), the co-applicant Novartis or Dana-Farber Cancer Institute made an application after confirming that the clinical trial results were excellent. However, there was a presentation of review paper which stated “the initial clinical results looked very exciting” before filing an application for use invention pharmaceutical for related to GIST, and as a result, the corresponding use invention for pharmaceutical related to GIST became invalidated due to the lack of inventive step. Referring to the above case, it seems safer to file an application based on in-vitro or in-vivo results without waiting for clinical trial results if it is the case of indication expansion for a specific compound.
Meanwhile, after the Supreme Court en banc decision on Entecavir rendered by the Supreme Court (the Supreme Court hu768 decision rendered on May 21, 2015), the administration method or administration dosage was acknowledged as an element. In addition, according to the Supreme Court decision on Rivastigmine rendered by the Supreme Court (the Supreme Court hu2702 decision rendered on Aug. 29, 2017), the inventive step can be acknowledged if a heterogeneous effect or a significant quantitative effect is proved through administration method or administration dosage.
Accordingly, the filing date of invention characterized by administration method or administration dosage among the use inventions for pharmaceutical became a crucial issue. However, because most of these administration methods or administration dosages are determined in clinical trials, especially in phase 2 clinical trials, there is no choice but to file an application based on clinical trial data. Therefore, it is desirable to file an application immediately after the efficacy is confirmed in the corresponding administration method or administration dosage, that is, after the primary end point, and the application should be finalized somehow immediately before being released to the media.
What patent practicians should consider.
Use inventions for pharmaceutical have very strict description requirements compared to substance inventions, and in particular, the practical business in Korea is stricter than that in other countries. Therefore, if the scope intended to acquire rights related thereto in use invention for pharmaceutical is clear, it is necessary to secure experimental data for such scope, and to make the inventor well aware of this point. If it is impossible to secure experimental data, there will eventually be a situation where the unconfirmed scope has to be waived.
In addition, pharmaceutical companies with new drug pipelines often consider use inventions for pharmaceutical as part of their life cycle management, and the biggest enemy of registrations of use invention for pharmaceutical is unexpectedly more often inside the company. Even if the expected or more than expected pharmacological effect is confirmed, it is not too late to express expectations or excitement after an application is filed based on a well-planned patent application strategy.
Lastly, the case of Gleevec-GIST teaches us that even if the details of use invention for pharmaceutical are not disclosed, but the contents giving hints on the pharmacological effect are disclosed, the applicable invention may be exposed to the risk of being invalidated apart from the value of such invention. Therefore, it is of utmost importance to control the internal divulging before filing an application at the time of completion of use invention for pharmaceutical.
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