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Intellectual Property High Court (IPHC) affirmed the inventive step of crystalline invention from the viewpoint of obstructive factors

1. Background
  The Defendant is the patentee of a patent for an invention named “microcrystal” (Patent No. 4606326, this patent is hereinafter referred to as “the Present Patent”).
  The Present Patent was filed as Japanese Patent Application No. 2005-506044 with an international filing date of May 7, 2004 (Domestic priority date: May 9, 2003), and registration of the Present Patent was established on October 15, 2010.
  On October 12, 2020, the Plaintiffs filed a request for patent invalidation trial regarding the Present Patent (number of claims: 5), and the Japan Patent Office (JPO) examined the case as Invalidation Trial No. 2020-800100. On June 7, 2020, the JPO issued a trial decision (hereinafter referred to as “the trial decision of the present case”) stating that “The request for a trial is dismissed.” Accordingly, the Plaintiffs instituted a lawsuit to seek rescission of the trial decision of the present case.
  The issues were whether or not there was an inventive step and whether or not there was a violation of the support requirements. The Intellectual Property High Court (IPHC) affirmed the trial decision, which found that there was an inventive step and there was no violation of the support requirements. Below, the inventive step is explained among these issues.

2. Inventions of Present Patent
  The statement of Claims of the Present Patent are as follows (hereinafter, the invention according to each claim is referred to in the manner of “Present Invention 1” in correspondence with the claim number, and Present Inventions 1 to 5 are collectively referred to as “the Present Invention”).
<Claim 1>
  Microcrystals of (E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione represented by the following formula

[Compound 1]

wherein the average particle size of the microcrystals is 0.5 to 20 µm, and the crystallinity is 40% or more.
<Claim 2>
  A solid pharmaceutical formulation comprising microcrystals of (E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione, wherein the average particle size of the microcrystals is 0.5 to 20 µm, and the crystallinity is 40% or more.
<Claim 3>
  The solid pharmaceutical formulation according to claim 2, wherein the microcrystals are obtained by pulverization of crystals of (E)-8-(3,4-dimethoxystryl)-1,3 -diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione.
<Claim 4>
  The solid pharmaceutical formulation according to claim 2, wherein the microcrystals are in a mixture obtained by mixing crystals of (E)-8-(3,4-dimethoxystryl)-1,3 -diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione and additives and pulverizing the resulting mixture.
<Claim 5>
  The solid pharmaceutical formulation according to claim 3 or 4, wherein the pulverization is a pulverization using a jet mill.

3. Trial Decision by the JPO
  The issues were whether or not there was an inventive step and whether or not there was a violation of the support requirements. The trial decision of the present case maintained this patent, stating that there was an inventive step and there was no violation of the support requirements. Below, the inventive step of Present Invention 1 is explained.

(1) Recognition of the inventions described in Exhibit Ko 1 (JP A 1994-211856)
  Exhibit Ko 1 describes the following inventions (hereinafter, the former invention is referred to as the “Ko 1 Crystal Invention” and the latter invention is referred to as the “Ko 1 Preparation Invention”).

(Ko 1 Crystal Invention)
A light-yellow needle crystal of (E)-8-(3,4-dimethoxystryl)-1,3-diethyl-7-methylxanthine
(Ko 1 Preparation Invention)
A solid pharmaceutical formulation comprising a light-yellow needle crystal of (E)-8-(3,4-dimethoxystryl)-1,3-diethyl-7-methylxanthine

(2) Comparison/Judgment
  Comparing Present Invention 1 and the Ko 1 Crystal Invention, they are the same in that they are “crystals of Compound 1”, and they differ in the following points.

(Difference 1)
Present Invention 1 specifies that the average grain size of a microcrystal is 0.5 to 20 μm, whereas the Ko 1 Crystal Invention does not specify the average grain size and does not clarify if it is a microcrystal.

(Difference 2)
Present Invention 1 specifies that the crystallinity is 40% or more, whereas the Ko 1 Crystal Invention does not specify the crystallinity.

* Comparison/Judgment regarding Present Inventions 2 to 5 is omitted.

4. Decision of the IPHC
4-1. Issues recognized from Ko 1 Crystal Invention
(1) Solubility
  The IPHC stated that the Ko 1 Crystal Invention itself does not immediately lead to the issue of increasing the solubility of the crystals of Compound 1, and there is no other description or suggestion regarding the issue in Exhibit Ko 1.
  However, the IPHC stated that at the time of this priority date it was a well-known issue for those skilled in the art to increase the solubility of poorly water-soluble drugs for oral administration in order to improve their absorption and bioavailability. According to Exhibit Ko 1, the Ko 1 Crystal Invention (crystals of Compound 1) is also used for oral administration. A person skilled in the art at the time of the priority date recognized that the crystals of Compound 1 had low solubility.
  Accordingly, the IPHC determined that a person skilled in the art at the time of the priority date who found the Ko 1 Crystal Invention would have recognized the problem of increasing the solubility of the Ko 1 Crystal Invention (crystals of Compound 1).

(2) Stability
  The IPHC stated that the Ko 1 Crystal Invention itself does not immediately lead to the issue of increasing the stability of the crystals of Compound 1, and there is no other description or suggestion regarding the issue in Exhibit Ko 1.
  However, the IPHC stated that according to other Exhibit Ko, increasing the stability of drugs was an obvious issue for those skilled in the art at the time of the priority date.
  Accordingly, the IPHC determined that a person skilled in the art at the time of the priority date who found the Ko 1 Crystal Invention would have recognized the problem of increasing the stability of the Ko 1 Crystal Invention (crystals of Compound 1).

4-2. Decreasing the average particle size of the crystals of Compound 1 and increasing the crystallinity of the crystals of Compound 1
(1) Solubility
  The IPHC determined that as methods to increase the solubility of poorly water-soluble drugs for oral administration, “reducing the particle size of the crystals by pulverization”, “changing the crystal form to an unstable or metastable form”, “reducing the crystallinity of the crystals”, etc. were well-known techniques at the time of the priority date of this case.

(2) Stability
  The IPHC determined that as methods to increase the stability of poorly water-soluble drugs for oral administration, “increasing the crystallinity of crystals”, “forming a protective coating on a drug for the purpose of blocking light, moisture, etc.”, “coating with a coating liquid containing a light blocking agent (titanium oxide) for the purpose of blocking light”, etc. were well-known techniques at the time of the priority date of this case.

4-2. Combination of well-known techniques (obstructive factors)
  The IPHC stated that at the time of the priority date of this case, there was common technical knowledge that amorphous drugs generally have higher solubility, and therefore, for the purpose of improving the solubility of poorly water-soluble drugs, the crystallinity was commonly lowered instead.
  Also, the IPHC stated that at the time of the priority date of this case, there were well-known techniques for increasing the solubility of poorly water-soluble drugs for oral administration other than reducing the particle size of crystals, and there were also well-known techniques for increasing the stability of drugs other than increasing the crystallinity of crystals.
  The IPHC determined that adopting a well-known technique for increasing the solubility of poorly water-soluble drugs for oral administration (well-known technique of reducing the particle size of crystals) from the perspective of pursuing the solubility of Compound 1, and also deliberately adopting a well-known technique that could result in decreasing the solubility of the drug (a well-known technique of increasing the crystallinity of the crystal) from the perspective of pursuing the stability of Compound 1 could not have been easily conceived by a person skilled in the art at the time of the priority date who recognized the issues of increasing the solubility and stability of Compound 1.

4-3. Conclusion
  The IPHC determined that it would not have been easy for a person skilled in the art at the time of the priority date who recognized the issues of the Ko 1 Crystal Invention, increasing the solubility and stability of Compound 1, to set the average particle size of the crystals of Compound 1 in the numerical range of Difference 1 and the crystallinity in the numerical range of Difference 2. Accordingly, the inventive step of Invention 1 was affirmed. In addition, the inventive steps of Inventions 2 to 5 were similarly affirmed.

5. Comments
  In this judgment, the inventive step was affirmed, as a combination of well-known techniques that have contradictory effects cannot be easily conceived. One of the reasons for affirming the inventive step is “obstructive factors,” and this judgment seems to have adopted the obstructive factors.
  In this case, the IPHC determined that adopting a well-known technique for reducing the particle size of crystals from the perspective of pursuing the solubility of Compound 1, and also deliberately adopting a well-known technique that increases the crystallinity of the crystal (well-known technique that can result in decreased drug solubility) from the perspective of pursuing the stability of Compound 1 could not have been easily conceived.
  In the future, combination of well-known techniques with contradictory effects may be recognized as affirming inventive step, and this will be a reference in future practice.
  The Examination Guidelines also indicate “obstructive factors” as one of the factors in support of the existence of an inventive step. However, they also indicate “if it is sufficiently reasoned that a person skilled in the art would easily conceive the claimed invention after considering the obstructive factor, the claimed invention does not involve an inventive step”. It should be noted that obstructive factors should be considered not only from the viewpoint of “a combination of well-known techniques with contradictory effects” but also from the viewpoint of whether or not a person skilled in the art could have easily conceived the invention.
  In order to further clarify the judgment on this case, it is necessary to accumulate judicial precedents, and it is important to watch future trends of the judicial precedents.

https://www.ip.courts.go.jp/app/files/hanrei_jp/206/092206_hanrei.pdf