Takeda’s dexlansoprazole patent found invalid for lack of sound prediction of utility and for insufficiency
Background
The drug DEXILANT is used to treat heartburn associated with gastroesophageal reflux disease and to heal damage to the esophagus from stomach acid. In Takeda Canada Inc. v. Apotex Inc., an action pursuant to section 6(2) of the Patented Medicines (Notice of Compliance) Regulations, Takeda argued that Apotex’s dexlansoprazole oral dose capsules would infringe the asserted claims of Canadian Patent No. 2,570,916.
This post focuses on the Federal Court’s findings with regard to the validity of the 916 Patent. Aitken Klee’s blog post on the Court’s reasons on infringement can be found here.
The Court found the following essential elements of Claim 1 of the 916 Patent, on which the other asserted claims depended:
- A dosage form that includes a PPI;
- The PPI is released as a first and a second dose;
- The first and second dose are released as discrete pulses;
- Each pulse of the PPI is sufficient to raise plasma concentrations above a threshold concentration of at least 100 ng/mL;
- The second dose contains at least 10% more of the PPI than the first dose; and
- The first and the second dose independently comprise between 5 mg and 300 mg of the PPI.
Invalidity
Anticipation and Obviousness
The Court found that, contrary to Apotex’s arguments, the 574 Application did not anticipate the asserted claims. In addition, the asserted claims were not obvious in light of the state of the art.
Utility
The Court examined whether there was a sound prediction of the utility of the asserted claims—which the parties agreed was the use of a dosage form with the claimed PK profile to give a pharmacological effect—by the filing date of the 916 Patent.
Apotex’s expert identified a fatal assumption in the disclosure of the 916 Patent: the patent equated the effect compartment concentrations to the steady state plasma concentrations, when a direct correlation between these two concentrations does not exist. Apotex’s expert also highlighted that the modelling in the disclosure of the 916 Patent was based on data from IV administration, not from an oral dosage form with two doses releasing as two pulses of PPI.
The inventors of the 916 Patent had modelled the oral dosing data to simulate the impact of dual-pulse dosing regimens. This modelling was not referenced in the 916 Patent.
The Court found that the effect of the pulsatile release dosage form could not be predicted until the oral data simulations were conducted. The data from the oral dosage modelling was not included in the 916 Patent and the common general knowledge did not include the pulsatile release dosage forms of PPIs. “Without this data in the 916 Patent, the PSA would not have the line of reasoning used by the inventors to predict that the dosage form proposed would achieve the practical utility and would not be able to fill that gap with their CGK.”
As a result, the Court concluded that the asserted claims are invalid because the disclosure of the 916 Patent does not support a sound prediction of utility. This finding is linked to the Court’s conclusion on insufficiency.
Insufficiency
The Court identified two deficiencies in the disclosure of the 916 Patent:
- The data in the disclosure was not sufficient for the person skilled in the art to understand how the inventors determined the oral dosage data and steady state plasma concentrations; the modelled data in the disclosure would have been known to be significantly lower than the actual steady state plasma concentrations and the data was from an IV study and did not include subsequent oral dosage modelling data.
- The disclosure of the 916 Patent did not teach any particular dosage form that would satisfy the asserted claims; to determine if the parameters of the asserted claims are met, the person skilled in the art would have to conduct experimentation to identify potential options for formulating a dosage form.
The experts before the Court agreed that the experimentation work would include a significant number of steps to arrive at the invention, including administration of the dosage form to humans and performing dose adjustments to determine dose amounts.
The Court found that the work required to determine the missing information was much more than anticipated in the Patent Act and involved at least as much work as in Teva Canada Ltd. v. Pfizer Canada Inc., in which the Supreme Court of Canada had found the disclosure was insufficient because the work required “administering the compounds to humans and monitoring the pharmacological response of such experimentation.” The Court concluded the disclosure of the 916 Patent was insufficient.
Overbreadth
Apotex argued that the claims were overbroad because at least 1 hour was required between the pulsed doses, but this 1 hour gap was not claimed. The Court disagreed. The evidence did not support that there must be any particular time gap, only that some time gaps were more desirable than others. In addition, the use of the term “discrete” in the asserted claims indicated that there was some noticeable time period between the pulses.
Ambiguity
The Court dismissed Apotex’s assertion that the claims were ambiguous. The asserted claims were indisputably capable of being constructed; that the parties disputed the meaning of certain terms did not render the claims ambiguous.
Unpatentable subject-matter
Apotex argued the asserted claims were aimed at a desired result (any pulsed release dosage form that achieves the claimed pharmacokinetic result) and not a novel dosage form. The Court disagreed and found that the asserted claims related to a physical dosage form. Because this was a vendible product, the asserted claims were not directed to unpatentable subject matter.
Conclusion
The Court concluded that the asserted claims were invalid for lack of sound prediction of utility and for insufficiency.
A copy of the decision in 2024 FCA 106 is available here.
