On June 17, 2020, the Intellectual Property High Court (the "IP High Court") held that an invention regarding a composition for treating allergic eye disorder has a remarkable effect and has inventive step stating that a previous IP High Court judgment deciding that the same invention lacked inventive step does not bind the later Court on the issue of remarkable effect of the invention.
(IP High Court Case No. 2019 (Gyo-ke) 10118)
Background
Alcon Laboratories Incorporated and Kyowa Hakko Kirin co-own a patent (the "Patent") regarding a composition for treating allergic eye disorder which includes Compound A (11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid). Company X filed an invalidation trial against the Patent.
The invention claimed in Claim 1 of the Patent (the "Invention") is as follows:
A human conjunctival mast cell stabilizer for ophthalmic use prepared as a topically administered ophthalmic eye drop for the treatment of allergic eye diseases in humans,
comprising a therapeutically effective amount of Compound A or a pharmaceutically acceptable salt thereof.
This case went back and forth between the JPO and the IP High Court and the first three decisions of the JPO trial board were remanded by the IP High Court. Furthermore, the third IP High Court judgement was cancelled and remanded by the Supreme Court as explained below.
The IP High Court cancelled the JPO's Second Decision which found that the invention was not obvious based on prior art references 1 and 2 and remanded the case to the JPO, finding that it would have been easy to conceive of the Invention based on prior art references 1 and 2 (the “Previous IP High Court Judgment”).
The IP High Court, in a later case, also cancelled the JPO's Third Decision which maintained the validity of the Patent because of the existence of a remarkable effect even though it would have been easy to conceive of the invention based on prior art references 1 and 2. The IP High Court, in this case, found that a person skilled in the art would have been able to predict the effect of Compound A based on prior art references 1 and 2 in combination with other prior arts disclosing other compounds (such as Ketotifen, Procaterol Hydrochloride, Disodium Cromoglycate and Pemirolast potassium) that showed a high inhibitory effect on histamine release from human conjunctival mast cells as of the priority date.
On appeal, the Supreme Court decided that the IP High Court had erred by simply assuming that it would have been obvious to use the claimed compound for the intended purpose of the invention (i.e. human conjunctival mast cell stabilizer) without adequately considering
(a) whether the effect exhibited by the invention in its specific configuration could not have been predicted by a person skilled in the art; and
(b) whether the effect is a remarkable effect that goes beyond a range that could be predicted by a person skilled in the art.
The case went back to the IP High Court.
Judgement
1. The IP High Court held in relation to the inventive step as follows.
(1) The Previous IP High Court judgment stated that for each invention in this case there is a motivation to reach the structure of the Invention. However, even if there is a motivation to reach the structure of the Invention, if the Invention has a remarkable effect that goes beyond a range that could be predicted by a person skilled in the art as of the priority date, a person skilled in the art would not have easily conceived of the Invention.
Because it can be understood that the Previous IP High Court Judgment did not judge whether the Invention has such a remarkable effect that could not be predicted by a person skilled in the art, the previous judgment is not binding on that point (Article 33(1) of Administrative Case Litigation Act).
(2) Compound A of the Invention has an effect that the inhibition rate of histamine release from human conjunctival mast cells increases in a concentration-dependent manner between 30 μM and 2000 μM, reaching a maximum value of 92.6%. And between these concentrations, unlike Cromolyn Sodium and Nedocromil Sodium, no decrease in the inhibition rate occurred at concentrations higher than the one at which the inhibition rate reached the maximum value. The effect of Compound A as mentioned above had not been obvious as of the priority date.
2. The IP High Court rejected the argument that the effect of the Invention can be predicted from similar substances as follows.
(1) In prior art reference 1, the experimental results of Ketotifen used on guinea pigs did not show significant inhibition of the release of histamine from the conjunctiva of guinea pigs. In contrast to the results of experiments in guinea pigs, Ketotifen can be used as a stabilizer of human conjunctival mast cells in humans, and the rate of inhibition of histamine release in humans is 67.5% (5 minutes after the induction of allergic reaction) and 67.2% (10 minutes after the induction of allergic reaction).
However, there was no evidence that as of the priority date Ketotifen inhibited the release of histamine from human conjunctival cells between 30 μM and 2000 μM in a concentration-dependent manner.
(2) There is no evidence that Chlorpheniramine (which was said to have no effect on the release of histamine in the conjunctiva of guinea pigs, the same as Compound A of the Invention and Ketotifen) was, as of the priority date, known to have a stabilizing effect on human conjunctival mast cells.
(3) Amelexanox (which is an antiallergic agent having a tricyclic skeleton like Compound A and Ketotifen) has a significant inhibitory effect on the release of histamine from the conjunctiva of guinea pigs, whereas Compound A does not show a significant effect.
Moreover, Nedocromil Sodium (which is an antiallergic agent having a tricyclic skeleton like Compound A and Ketotifen) hardly stabilizes human conjunctival mast cells in an experiment on a cell population in which the cells are cultured (Table 1 of the specification of the Patent), whereas Compound A has a significant stabilizing effect on human conjunctival mast cells in the same experiment.
Considering these differences between Amelexanox / Nedocromil Sodium and Compound A, it cannot be said that substances having the same structure - tricyclic skeleton – would have the same degree of efficacy.
(4) Furthermore, while Ketotifen was used in various experiments in prior art reference 1 for comparison with Compound A and was listed side by side with Compound A, because the ring structures and substituents thereof are different, a person skilled in the art would not have understood that Compound A has the same degree of histamine release inhibitory effect as Ketotifen does.
(5) Therefore, a person skilled in the art who read the description of prior art reference 1 could not predict the effect on human conjunctival mast cells of Compound A which is described in 1 (2) above even if a person skilled in the art understood the effect of Ketotifen.
(6) Compound A, Procaterol Hydrochloride, Disodium Cromoglycate, and Pemirolast potassium have remarkably different chemical structures. Furthermore, the inhibitory effect on histamine release would differ depending on the chemical structure. Therefore, a person skilled in the art could not predict that Compound A has the same degree of stabilizing effect on human conjunctival mast cells that those compounds above have.
3. In conclusion, the IP High Court found that since the Invention has a remarkable effect that goes beyond a range that would have been able to predict by a person skilled in the art from the structure of the Invention, the Invention would not have been easily conceived by a person skilled in the art.
Comments
1 Whether the Previous IP High Court Judgement is binding on this Court or not.
Article 33(1) of the Administrative Case Litigation Act stipulates as follows;
A judgment to revoke an original administrative disposition or administrative disposition on appeal shall be binding on the administrative agency that has made the original administrative disposition or administrative disposition on appeal and any other relevant administrative agency with regard to the case.
Therefore, If the IP High Court cancels a JPO decision, the Examiner of the JPO cannot make a decision that is inconsistent with the main text and fact findings and legal decisions indispensable for the main text of the judgement by the IP High Court.
Although the JPO, in its Third Decision, found the Invention to have inventive step because of its remarkable effect, the Previous IP High Court Judgment had already judged that a person skilled in the art would have easily conceived of the Invention from the prior art references. However, this IP High Court Judgement showed that the Previous IP High Court Judgement is not binding because it has not decided whether the Invention has a remarkable effect or not, even if it denied the inventive step due to the existence of a motivation to the structure of the Invention.
2 The relationship between easiness of combination and remarkable effect
Concerning how to consider the “remarkable effect” in the inventive step, there are two contending positions among scholars. The first group say that inventive step should be satisfied if the invention has a remarkable effect, even though specific configuration of the invention could have been easily arrived by a person skilled in the art. The second group say that the remarkable effect is one of factors to be taken into account in determining whether a person skilled in the art would have been able to easily conceive that invention based on prior art.
This judgement seems to take the former position because of the following reason.
While the Previous IP High Court Judgement has already said a person skilled in the art would have been able to easily conceive the Invention based on the prior art reference and has no inventive step, the later IP High Court also judged on the inventive step including the remarkable effect. This shows that the IP High Court found that the existence of a remarkable effect can be an independent reason for satisfying the inventive step of the Invention.
3 How to examine a remarkable effect
The Supreme Court decision held that, in order to determine whether the inventive step is satisfied or not, it is needed to consider whether the effect of an invention is remarkable in view of (i) whether, as of the priority date, the effect exhibited by the invention in its specific configuration could not have been predicted by a person skilled in the art, and (ii) whether the effect is a remarkable effect that goes beyond a range that could be predicted by a person skilled in the art.
In light of this Supreme Court decision, the IP High Court fully examined prior art references and held that a person skilled in the art could not predict the remarkable effect of Compound A from the effect of Ketotifen or other compounds.
In the field of chemistry, pharmaceuticals and biology, it might be difficult to predict the activity of substances from the structure in the first place. Actually, this IP High Court Decision fully examined and acknowledged the remarkable effect in the field of pharmaceuticals. This IP High Court decision shows how the court will determine a remarkable effect under the guidance given by the Supreme Court.
4 Conclusion
The Examination Guidelines for Patent of the JPO and some previous precedents have shown that a remarkable effect should be taken into account as a factor in determining whether a person skilled in the art would have been able to easily conceive that invention based on prior art, unlike this IP High Court Decision. Thus, there still could be contending positions regarding how to consider a remarkable effect and this issue has not been determined yet.
It would be interesting to see whether other courts in other cases would follow the position of this judgement or take other position such as the Examination Guideline and some previous precedents regarding remarkable effect.
Written by Mr. Kota Yamada (Attorney at law)