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      On May 25, 2015, the Defendant filed a patent application for an invention of “PTH-containing therapeutic/prophylactic agent for osteoporosis, characterized in that PTH is administered once a week in a dose of 100 to 200 units” (Japanese Patent Application No. 2015-105266; a divisional application of Japanese Patent Application No. 2011-530844 filed on September 8, 2010 [priority date: September 9, 2009] filed as a national entry application of a PCT application), and obtained a patent on September 1, 2017 (Patent No. 6198346; which is hereinafter referred to as “the patent”).

      On August 29, 2019, the Plaintiff filed a request for an invalidation trial with regard to Claims 1 and 2 of the patent (Invalidation Trial No. 2019-800062).

      On August 11, 2021, the JPO allowed correction for Claim 2, and rendered a JPO Decision that the request for the invalidation trial was groundless.  On September 16, 2021, the Plaintiff filed a lawsuit at IP High Court (IPHC) seeking rescission of the JPO Decision.

      One of the issues of the lawsuit was whether or not there was an inventive step, and the IPHC rescinded the JPO Decision that there was an inventive step.

 

      After the correction, the patent includes Claim 1 and Claim 2 (hereinafter referred to as “Invention 1” and “Invention 2”, respectively), and Claim 1 recites the following:

      An agent for the treatment or prevention of osteoporosis for the inhibition of bone fractures that contains PTH (1 -34) or a salt thereof as an active ingredient, characterized in that PTH (1-34) or the salt is administered once a week in a dose of 200 units over a duration exceeding 48 weeks to 72 weeks or longer, to treat osteoporosis patients who satisfy all of the following conditions (1) to (3):

      (1) age of 65 years or older

      (2) prevalent bone fractures

      (3) bone density not more than 80% of average done density of young adult and/or degree of bone atrophy of I or higher.

 

      Differences between Invention 1 and Exhibit Ko 1 Invention, which is a primary prior art, are as follows.

(Difference 1)

      In Invention 1, the “osteoporosis patients” are “osteoporosis patients who satisfy all of the following conditions (1) to (3):

      (1) age of 65 years or older

      (2) prevalent bone fractures

      (3) bone density not more than 80% of average bone density of young adult and/or degree of bone atrophy of I or higher,”

      whereas in Exhibit Ko 1 Invention, the patients are “subjects of the ages between 45 and 95 years who were defined as osteoporosis patients based on the diagnostic criteria proposed by a Committee supported by the Ministry of Health and Welfare, with a total score higher than 4 as a result of defining osteoporosis in terms of multiple factors weighted in the form of scores.”

(Difference 2)

      The “therapeutic or prophylactic agent for osteoporosis” is specified to be “for the inhibition of the bone fractures” in Invention 1, whereas there is no such specification in Exhibit Ko 1 Invention.

(Difference 3)

      The agent is specified to be “administered … over a duration exceeding 48 weeks to 72 weeks or longer” in Invention 1, whereas there is no such specification in Exhibit Ko 1 Invention.  (The tests in Exhibit Ko 1 Invention are for administration up to 48 weeks.) 

 

      The IPHC held that, because Invention 1 having the Differences 1 to 3 would have been easily conceived by a person skilled in the art, there was an error in the JPO Decision which found that Invention 1 involves an inventive step.  The IPHC further ruled that there was also an error in the JPO Decision which found that Invention 2 involves an inventive step on the basis that Invention 1 involves an inventive step.  The outline of judgment of the IPHC regarding Differences 1 to 3 is as follows.

 

(1)  Regarding Difference 1

      The conditions of Invention 1 are “(1) age of 65 years or older” (Condition (1)), “(2) prevalent bone fractures” (Condition (2)), and “(3) bone density not more than 80% of average bone density of young adult and/or degree of bone atrophy of I or higher” (Condition (3)).  Since Conditions (2) and (3) are the same as conditions applied for the diagnosis of osteoporosis under the diagnostic criteria of Exhibit Ko 5, it is not difficult at all for a person skilled in the art to apply Conditions (2) and (3) for screening osteoporosis patients to whom the therapeutic agent for osteoporosis is to be administered once a week in a dose of 200 units as referred to in Exhibit Ko 1 Invention.

      In addition, since there is a common general technical knowledge that the incidence of osteoporosis increases with age, it is only a natural choice and not difficult at all for a person skilled in the art to apply, in addition to Conditions (2) and (3), a condition similar to Condition (1) specifying that the osteoporosis patients to be administered the agent are those aged 65 or older, by focusing on the fact that the age is indicated, along with the low bone density and the prevalent bone fractures, as the multiple risk factors for the bone fractures caused by osteoporosis.

 

(2)  Regarding Difference 2

      Osteoporosis is a bone disease characterized by decreased bone strength and involves an increased risk for the bone fractures, and the purpose of the treatment of osteoporosis is to prevent the bone fractures; and there was a common general technical knowledge that “bone strength” consists of two factors—bone density and bone quality—and that the bone density accounts for almost 70% of the bone strength.  According to this knowledge, a person skilled in the art would understand the fact that increase in the bone density contributes to prevention of bone fractures.

      Then, it follows that a person skilled in the art would have easily conceived of using the osteoporosis therapeutic agent referred to in Exhibit Ko 1 Invention for the inhibition of bone fractures.

 

(3)  Regarding Difference 3

      According to the specification of the patent, it is difficult to find the critical significance in “48 weeks” and “72 weeks or longer,” and no particular technical meaning can be found in the limitation which defines the start and the end of a period specified by “a duration exceeding 48 weeks to 72 weeks or longer.”  Such limitation merely means that the specified period indicates that the bone fracture incidence declined as the PTH administration was continued over a discretionary period.

      As of the reference date for determining the patentability of Invention 1, it was known that the bone density increases and the incidence of bone fractures decreases through daily administration of a PTH preparation over a duration exceeding 48 weeks.

      Based on the report concerning the daily administration of PTH over a duration exceeding 48 weeks, which resulted in the increase in the bone density and the decrease in the incidence of the bone fractures, a person skilled in the art would have easily conceived of also administering the therapeutic agent for osteoporosis referred to in Exhibit Ko 1 Invention over a duration exceeding 48 weeks for increasing the bone density and preventing the bone fractures.

 

(4)  Considerations of effect of invention

      Regarding whether or not an effect of an invention is unpredictable and remarkable, the effect should be examined from the perspectives of whether the effect is one that a person skilled in the art would not have predicted as an effect provided by a structure of the invention as of the reference date for determining the patentability of the invention and whether the effect is a remarkable one that goes beyond the scope of effect that a person skilled in the art would have predicted based on the structure of the invention (see the Supreme Court Judgment, 2018 (Gyo-Hi) 69, rendered on August 27, 2019).  Indeed, since it is difficult to determine whether the invention provides an unpredictable and remarkable effect solely from the structure of the invention, it is regarded to be permissible to take into consideration an effect provided by the prior art having a structure similar to that of the invention or a similar effect achieved by the state of the art at that time.  Meanwhile, the burden of proof regarding the unpredictable and remarkable effect lies on the patentee.  It is noted that, even if the effect provided by the structure of the invention is unknown, it cannot be immediately concluded that the invention provides an unpredictable and remarkable effect.

 

(5)  Effect of Invention 1

      The unpredictable and remarkable effects of Invention 1 asserted by the plaintiff are as follows:

        [i] outstanding effect of inhibiting the bone fractures, indicating a 79% relative risk reduction (RRR) in comparison to placebo, after 72 weeks (Effect [i]);

        [ii] effect of intensifying the bone fracture inhibiting effect through continuous administration of the agent (Effect [ii]); and

        [iii] effect of substantially completely inhibiting bone fractures after 48 weeks (Effect [iii]).

 

(5-1) Regarding Effect [i]

      In order to confirm Effect [i], there is a need to compare the inhibitory effect on bone fractures in high-risk patients (patients who satisfy all of the Three Conditions) with that in low-risk patients (patients who do not satisfy all or a part of the Three Conditions).  However, it cannot be concluded from the disclosure of the specification that the degree to which the bone fracture occurrence of the high-risk patients is inhibited is higher compared to such degree of the low-risk patients.  According to the above, Effect [i] is not based on the disclosure of the specification.

 

(5-2) Regarding Effect [ii]

      According to the specification of the patent, the patients to whom the osteoporosis therapeutic agent of Invention 1 was administered were merely compared with the patients to whom a placebo was administered, and it does not indicate that the inhibitory effect on the bone fractures is higher in the patients who satisfy all of the Three Conditions than in the patients who do not.  In addition, Exhibit Ko 2 describes that, when 20 or 40 μg of PTH was administered daily for an average of 17 or 18 months, the rate of the bone fracture inhibition by the PTH administration became higher as the administration period became longer.  Therefore, it was within the expectation for a person skilled in the art that the inhibitory effect on the bone fractures would be intensified through the continuous administration of the agent.

 

(5-3) Regarding Effect [iii]

      Effect [iii] only means a fact as a test result that no new vertebral fractures were found when the administration went beyond 48 weeks, which can hardly be found to mean that the osteoporosis therapeutic agent of Invention 1 is a therapeutic agent that completely inhibits bone fractures in practice after 48 weeks of administration (a complete wonder drug).  The Defendant also does not allege that the osteoporosis therapeutic agent of Invention 1 provides such effect.  When considering that no vertebral fractures were found during 48-week administration also in Exhibit Ko 1 Invention, it can be understood that the bone fracture incidence was originally low.  Accordingly, even if the number of bone fractures during the period exceeding 48 weeks to 72 weeks was zero in Invention 1, such zero number was not surprising for a person skilled in the art, and it is within the scope of expectation for a person skilled in the art.

 

      The Judgment, as requirements of the inventive step of medicinal inventions, indicated considerations as to the numerical limitations and so on.

      The numerical limitation of the age of the patients to be administered (65 years old or older) was examined based on the common general technical knowledge such as the relationship between disease and age, and then the inventive step was denied.  Regarding the relationship between the disease and the age, it is important to sufficiently make the prior art search, including common general technical knowledge, and then consider how the numerical value of the age should be limited in claims.

      It was held that the numerical limitation of the administration period (from 48 weeks to 72 weeks or more) has no critical significance in the specification of the patent.  From now on, it is necessary to prepare a specification in such a way that a critical significance in the numerical limitation of the administration period can be found in the specification. 

      Effects of Invention 1 have also been examined, and the specification indicates certain extents of Effect [i] and Effect [ii] for limited osteoporotic patients who satisfy all of the Three Conditions (Three Condition-satisfying patients).  However, the assertion based on the unexpected and remarkable effects was not accepted because of no comparison of the effects between the Three Condition-satisfying patients and non-satisfying patients in the specification.  From now on, it is necessary to choose working examples and comparative examples that can demonstrate unexpected and remarkable effects and disclose them in the specification.

      Regarding Effect 3, the IPHC made a strict decision stating that even if the number of the bone fractures during the period exceeding 48 weeks to 72 weeks was zero in Invention 1, such zero number itself was not surprising and was expected for a person skilled in the art.  In addition, with respect to the unpredictable and remarkable effects, the IPHC stated that since it is difficult to determine whether the invention has an unpredictable and remarkable effect solely from the structure of the invention, it is permissible to take into consideration an effect provided by the prior art having a structure similar to the invention or a similar effect that had been achieved by the state of the art at the time of the invention.  From now on, it is important to stress an unpredictable and remarkable effect by examining an effect provided by the prior art having a structure similar to the invention or a similar effect that had been achieved by the state of the art at the time of the invention.

      In addition, in order to further clarify the matters in this judgment, it is necessary to accumulate judicial precedents, and it is important to watch future trends in the judgments.

 

 

      In IPHC 2021 (Gyo-ke) 10069 on June 22, 2022, the rescission of this JPO Decision was discussed, and a similar judgment as in the present Judgment was held with respect to Difference 1 and Difference 2. (https://www.ip.courts.go.jp/app/files/hanrei_jp/346/091346_hanrei.pdf)