Eye spy prior art: Obviousness is central to decision in Allergan v Juno, 2023 FC 1686

Allergan and Abbvie brought this action under the PM(NOC) Regulations,^[1] seeking to prevent the issuance of a Notice of Compliance for Juno Pharmaceuticals' generic version of Allergan's LUMIGAN RC product. Allergan alleged Juno's product would infringe Canadian Patent No 2,585,691 (the 691 Patent). Juno admitted that its product would infringe, but counter-claimed that Claim 16 and dependent Claim 19 of the 691 Patent were invalid on the grounds of obviousness and insufficiency.

The formulation and use of LUMIGAN RC are given by Claims 16 and 19 of the 691 Patent, respectively,

16. A composition comprising by weight 0.01% bimatoprost, 0.02% benzalkonium chloride (BAK), 0.268% sodium phosphate dibasic heptahydrate, 0.014% citric acid monohydrate, 0.81% sodium chloride, water, and wherein said composition is an aqueous liquid with a pH adjusted to 7.3.

19. Use of a composition according to any one of claims 1 to 16 for treating glaucoma or intraocular hypertension in a mammal.

Bimatoprost is known to reduce inter-ocular pressure. BAK is generally used as a preservative in formulations, though is known to be cytotoxic. However, bimatoprost can cause eye irritation, hyperemia, and other side effects such that a formulation with reduced bimatoprost may reduce the frequency and severity of side effects. Allergan's LUMIGAN RC, the formulation of Claim 16, offers a new formulation over Allergan's prior product, LUMIGAN. LUMIGAN contains 0.3% bimatoprost (3 times more than LUMIGAN RC) and 0.005% BAK (4 times less than LUMIGAN RC).

Claim construction was not in dispute. The parties agreed and the Court found that the claims should be read in accordance with their plain meaning as there are no terms in the claims that the person of skill would not understand. Therefore, recourse to the specification was not required. Claim 16 was found to be the composition of 0.01% bimatoprost (the skilled person would appreciate 0.01% to mean 100 ppm) and 0.02% BAK (the skilled person would appreciate 0.02% to mean 200 ppm) by weight with the pH adjusted to 7.3 to not irritate the eye.^[2] Claim 19 was to be the use of the formulated eye drops for treating glaucoma or intraocular hypertension in a mammal^.[3]

The invention was not obvious

The Court addressed obviousness through the four part test as described by the SCC in Apotex v Sanofi.^[4] Identifying or construing the inventive concept of Claims 16 and 19 was the key dispute between the parties. The Court found that the claims, as construed, did not reveal the inventive concept – the claims were simply to the formulation and use of the formulation, and did not disclose what was inventive of each. The Court used the specification to inform its construction of the inventive concept and determined that the inventive concept of Claim 16 (and therefore dependent Claim 19) included comparable efficacy to LUMIGAN in reducing inter-ocular pressure (IOP) while using less bimatoprost.^[5] This was achieved through an increased amount of BAK in the formulation that acts as a penetration enhancer.

In identifying the differences between the state-of-the-art and the inventive concept, the Court summarized:

[319] I find there were significant differences between the state of the art and the inventive concept. I agree with Allergan's description of these differences:

First, the prior art did not teach that reducing the concentration of bimatoprost from 0.03% to 0.01% could result in equivalent efficacy. Instead, the prior art taught that the efficacy of 0.01% bimatoprost would be worse. Second, the prior art taught to reduce or eliminate BAK due to toxicity concerns. In contrast, the invention increased the concentration of BAK above the 50 ppm that was sufficient to preserve the old formulation. Third, although the prior art taught that BAK could potentially act as a penetration for certain drugs, it taught that BAK would not enhance penetration for a lipophilic compound like bimatoprost. The only prior art that tested bimatoprost with and without BAK showed BAK did not enhance penetration.

The Court found that the gap could only be bridged with inventiveness – the claims were not obvious in light of the prior art.^[6] The Court found the state-of-the-art taught that reducing the amount of bimatoprost in the formulation would reduce its efficacy below that of LUMIGAN,^[7] taught that there was no need to increase BAK concentration as a preservative or even taught to reduce BAK concentration,^[8] and did not teach BAK would be an effective penetration enhancer for bimatoprost or similar molecules.^[9] Additionally, the Court found that the inventor's course of conduct involved significant expenditures, time, and many unsuccessful formulation attempts before finding the invented formulation.^[10] The Court concluded,

[380] […] Among the factors I considered on this point, per Sanofi at paragraph 69, I find that:

• It was not more or less self-evident that what is being tried ought to work. There were many possible solutions to the problem to be solved that were known to the POSITA;
• The extent, nature and amount of effort required to achieve the invention was extensive. The work did not involve routine trials;
• There was a motive in the prior art to find the solution the patent addresses; and
• Allergan's actual course of conduct shows that it did not reach the invention "quickly, easily, directly and relatively inexpensively."

The patent's disclosure was sufficient

Juno also alleged that the patent's disclosure was insufficient – that it did not disclose and enable a skilled person to work the invention^.[11] The Court rejected all of Juno's arguments and found the patent to sufficiently disclosed the invention.^[12]

The Court found the skilled person would be aware of the ingredients in the claims, know how to use them in a formulation, and be able to administer the formulation to a patient for treatment. The Court stated that the law does not require the patent to disclose why BAK works as a penetration enhancer for bimatoprost.^[13] All that is required is the patent sufficiently disclose what is claimed – a formulation with similar or better efficacy in reducing IOP in comparison to LUMIGAN.^[14] The Court rejected Juno's argument that the patent failed to disclose efficacy with respect to lessening side effects. The Court stated that "[although] the underlying motivation to develop an enhanced LUMIGAN product was undoubtedly to reduce hyperemia, the 691 Patent does not make any claim in that regard and so the failure to disclose data about the reduction in the incidence of hyperemia is not pertinent."^[15]

Additionally, the Court found that while there is no disclosure of safety in the patent, there is no suggestion that the components are toxic as to not be effective for the disclosed use. The Court noted that patent sufficiency is not equated to regulatory approval.^[16] Further, the Court noted the rabbit studies disclosed in the patent were sufficient and regularly accepted as a prediction for clinical results in the field.^[17]