In a significant decision, the Patent Court recently confirmed that a generic product using a prodrug ester form of the active ingredient of AstraZeneca’s blockbuster type II diabetes drug Forxiga® (dapagliflozin) was within the scope of a compound patent covering dapagliflozin, even if the patent does not expressly mention the prodrug ester form. This decision is especially remarkable because the applicant deleted the term “prodrug esters” from the claims during the prosecution due to the Korean Intellectual Property Office’s (KIPO’s) rejection of the term on the grounds that it lacks clarity. However, after reviewing the totality of the circumstances, the Patent Court determined that the deletion of “prodrug esters” from the claims did not demonstrate intentional exclusion of all prodrug esters from the scope of the patent and affirmed that the generic prodrug ester was within the scope of equivalents under AstraZeneca’s patent.
This case followed other recent efforts by Korean generic companies to try to design around originator patents with generic products using different salt forms from the originally approved active ingredient, on the theory that the scope of a patent during the patent term extension (PTE) period must be limited to the exact salt form of the originally approved active ingredient. The Supreme Court ultimately rejected those efforts and affirmed that other salt forms are still within the scope of the patent as long as they involve the same pharmacological mechanism of action and are not difficult to conceive of or implement based on the originally approved salt form.
Following the decision by the courts, Dong-A ST tried a different approach to get around AstraZeneca’s Forxiga® patent, by developing a drug using a prodrug ester form of dapagliflozin (dapagliflozin formate) instead of a different salt form. A prodrug ester is a compound that has the same basic chemical structure as the underlying compound (dapagliflozin in this case) but adds an ester moiety to the compound, which is separated from the compound in the patient’s body after being ingested. As such, while a prodrug ester of a compound is structurally different from the underlying compound, once ingested, it results in the same compound exerting the drug’s pharmacological effect in the body, since the ester moiety is removed from the compound in the patient’s digestive tract. Dong-A ST filed a scope confirmation action at the Korean Intellectual Property Trial and Appeal Board (IPTAB) to obtain a ruling that its prodrug ester (the Compared Product) was outside the scope of AstraZeneca’s patent because it is structurally different and because the term “prodrug esters” was deleted from the claims during prosecution, and the IPTAB agreed.
However, upon appeal, the Patent Court rejected Dong-A ST’s position and held that even if the Compared Product was not explicitly mentioned, it is still within the scope of equivalents covered by the patent, because it uses the same problem-solving principle to achieve the same working effect as the patent, the substitution of different elements would not have been difficult to conceive of, and the substituted element was not intentionally excluded from the patent during prosecution. Regarding the ease of substitution, the Court noted that the ester form chosen by Dong-A ST (the formate) was structurally the simplest ester that could have been used and that other formate ester prodrugs were known in the art, and that the formate did not provide any remarkable pharmaceutical effects in this case, so would have been considered a candidate by a drug developer of average skill level. The Court also rejected that the deletion of “prodrug esters” meant that AstraZeneca had intended to exclude prodrug esters from the scope of the patent on the basis that counterparts in other jurisdictions continued to claim prodrug esters expressly, and the record established that it was KIPO’s practice at the relevant time not to allow the term “prodrug” in patent claims for formality-related reasons. The Court thus concluded that “prodrug ester” was merely a “functional expression” that the applicant deleted from the claims in order to quickly resolve KIPO’s rejection of the term, and not an indication that the applicant intended to substantively remove prodrug esters from the scope of the claims.
In rejecting Dong-A ST’s attempt to design around AstraZeneca’s Forxiga® compound patent using a prodrug form of dapagliflozin that had no real medical benefit or advantages over dapagliflozin itself, the Patent Court’s decision helps protect the core innovation of AstraZeneca’s patent, and thus represents a significant step in defending the value of innovative pharmaceutical products in Korea.