Tokyo district court pronounced on February 28, 2013, a court decision for a litigation filed by TAKEDA Pharmaceutical Company Ltd. (TAKEDA) against several generic companies due to infringement of TAKEDA’s two patents, Japanese Patents No. 3148973 and No. 3973280, which cover pharmaceutical compositions for treating type 2 diabetes comprising pioglitazone hydrochloride and an additional active agent such as an alpha-glucosidase inhibitor or a biguanide.  However, the Judges dismissed TAKEDA’s demand.  This court decision may be a good example for understanding Japanese patent practice regarding medicaments to be used in combination therapy.

As you may know a method of treating a disease of a human, which comprises a direct action to a human body, is not patentable subject matter under Japanese patent practice because such a method is deemed to lack industrial applicability.  A use claim of a medicament will be also deemed as a method for treating disease state of a human under Japanese patent practice, which is not patentable subject matter.  However, a pharmaceutical composition identified by a use of a combination of plural medicaments and/or by a specific regimen used for administering a pharmaceutical composition is deemed to be a patentable subject matter in Japan.  Therefore, in order to protect a therapeutic method using a combination of two or more medicaments and avoid receiving a reason for rejection due to lack of industrial applicability, drafting a pharmaceutical composition claim specified by the combination of medicaments is a common practice under Japanese patent practice.

TAKEDA had a basic Japanese patent which covered pioglitazone and a salt thereof such as pioglitazone hydrochloride that are used for treating type II diabetes.  “Actos” is TAKEDA’s brand name of pioglitazone hydrochloride tablets for treating type 2 diabetes.  However, after this patent expired in 2011, many generic companies have launched pioglitazone hydrochloride tablets for treating type 2 diabetes in Japan.  Pioglitazone hydrochloride tablets may be often used in combination with an alpha-glucosidase inhibitor such as voglibose or a biguanide such as metformine.  It is believed that TAKEDA intended to protect pioglitazone hydrochloride tablets by means of the aforementioned two Japanese patents.

One of the arguments in the present infringement case is whether the pioglitazone hydrochloride tablets marketed by the generic companies infringe the TAKEDA’s patents which relate to a pharmaceutical composition comprising a combination of pioglitazone hydrochloride and an additional active agent such as an alpha-glucosidase inhibitor, which is covered by Japanese Patents No. 3148973 and No. 3973280.  The generic companies launch pioglitazone hydrochloride tablets, but do not launch a pharmaceutical composition comprising a combination of pioglitazone hydrochloride and an additional active agent such as an alpha-glucosidase inhibitor.  However, as mentioned above, it is well known that pioglitazone hydrochloride tablets are often administered to a patient by a practitioner in combination with an additional medicament such as an alpha-glucosidase inhibitor and a biguanide.  In fact, in the package inserts of the pioglitazone hydrochloride tablets marketed by the generic companies, it is explicitly stated that the tablets may be used in combination with an additional agent such as alpha-glucosidase inhibitor and a biguanide.

One of TAKEDA’s assertions is that the pioglitazone hydrochloride tablets marketed by the generic companies constitute indirect infringement of the TAKEDA’s patents.  Indirect infringement is provisioned in Japanese Patent Law, Article 101.  Article 101 is provisioned as follows:

“Article 101  The following acts shall be deemed to constitute infringement of a patent right or an exclusive license:

(1) where a patent has been granted for an invention of a product, acts of producing, assigning, etc., importing or offering for assignment, etc. any product to be used exclusively for the producing of the said product as a business;

(2) where a patent has been granted for an invention of a product, acts of producing, assigning etc., importing or offering for assignment etc. any product (excluding those widely distributed within Japan) to be used for the producing of the said product and indispensible for the resolution of the problem by the said invention as a business, knowing that the said invention is a patented invention and the said product is used for the working of the invention;

...[(3) to (4) were omitted] ... ”

For the present case, pioglitazone hydrochloride tablets can be administered alone to a patient without combining an additional medicament such as a biguanide, and thus even if administering pioglitazone hydrochloride in combination with the aforementioned additional medicament is deemed as an activity of producing a medicament comprising these two active agents, it will be recognized that pioglitazone hydrochloride tablets are not used exclusively for the production of a pharmaceutical composition of the TAKEDA’s patents.  Therefore, the question is whether or not Article 101, Number (2) quoted above can be applied to the pioglitazone hydrochloride tablets marketed by the generic companies.

The Judges at the Tokyo district court state in the court decision as follows: The “any product ... indispensible for the resolution of the problem” described in Article 101, No. 2 should be considered as a technical element which is newly disclosed by the claimed invention and which is also a distinctive structure or component providing the characteristic technical means capable of solving the technical problem to be solved by the claimed invention.  The characteristic technical element, which solves the problem and is newly disclosed by the claimed invention, is the use of a special combination of pioglitazone and another agent such as alpha-glucosidase inhibitor for treating type 2 diabetes.  Pioglitazone hydrochloride tablets have already known to be used for treating type 2 diabetes before the priority date of the present patents independently of the problem to be solved by the claimed inventions of the present patents.  For an invention relating to a combination of a plurality of materials, which existed before the priority date of a patent, materials, which already existed, should be considered to not correspond to “any product ... indispensible for the resolution of the problem” unless there is any special reason such as why a material, which already existed, is produced and sold for use in carrying out the invention.  However, it cannot be said that the defendants’ products are produced for use in carrying out the claimed invention of the present patents.  Therefore, the activity of the defendants does not constitute indirect infringement of the present patents.

In light of the court decision, regrettably we have to say that, in Japan, if each of the medicaments used in combination therapy can be used alone, it will not be easy to protect any of the medicaments by using a patent which relates to a pharmaceutical composition to be used in combination therapy, comprising a combination of two or more aforementioned medicaments.