Allergan’s eyedrop patent withstands the Federal Court’s gaze

Allergan commenced a patent infringement action against Juno, alleging that Juno’s proposed bimatoprost product would infringe claims 16 and 19 of Allergan’s 691 Patent. Juno conceded infringement but alleged that the 691 Patent was invalid for obviousness and insufficiency.

The 691 Patent relates to a new formulation for Allergan’s bimatoprost product, LUMIGAN RC, for use in treating glaucoma or intraocular hypertension (IOH). Glaucoma and IOH are both characterized by elevated intraocular pressure (IOP) caused by an imbalance between inflow and outflow in the eye’s drainage mechanisms. Elevated IOP damages the optic nerve, leading to visual field disturbances and blindness. Reducing IOP is the most important goal in treating glaucoma and IOH. Bimatoprost is a prostamide, which reduces IOP by increasing outflow of aqueous humour.  The new formulation made two key changes to Allergan’s old LUMIGAN formulation: a significant reduction in the amount of bimatoprost API, and a significant increase in the amount of benzalkonium chloride (BAK), a preservative.

The parties did not dispute the identity of the skilled person or claim construction. The parties agreed that the 691 Patent was addressed to a skilled team comprising an ophthalmologist and a formulator, both with some knowledge and experience relating to glaucoma and IOH. With respect to claim construction, the parties agreed that the claims mean what they say:

• Claim 16: A formulation containing bimatoprost and BAK with common excipients at a common pH of 7.3.
• Claim 19: Use of an eyedrop formulated in accordance with claims 1-16 for treating glaucoma or IOH in a mammal.

Obviousness

Justice Pentney held that the asserted claims of the 691 Patent were not obvious.

The inventive concept of claim 16 was a key point of disagreement between the parties. Allergan argued that the inventive concept of claim 16 must be understood with reference to the specification, which described that the inventive concept of the new formulation was to achieve IOP reduction comparable to that delivered by old LUMIGAN. Juno argued that the inventive concept of claim 16 was simply the formulation as claimed.

Justice Pentney held that he was not bound by prior decisions on the inventive concepts of claims 16 and 19 made under the old PM(NOC) regime, which involved a different procedural framework and evidentiary process. Justice Pentney agreed with Allergan that several elements of the specification supported the view that the inventive concept of claim 16 included the new formulation being at least as effective as old LUMIGAN. This was evident from:

• The title of the patent, “Enhanced Bimatoprost Ophthalmic Solution”;
• The fact that several Examples used old LUMIGAN as the control in tests that examined penetration of different formulations into the aqueous humour; and
• The text accompanying several Examples made it clear that the inventors were comparing different formulations with old LUMIGAN.

Justice Pentney concluded that the inventive concept of claim 16 was a formulation with less bimatoprost, but with comparable efficacy to old LUMIGAN, achieved by including more BAK than is found in old LUMIGAN. The inventive concept of claim 19 was the use of the formulation for the treatment of glaucoma and IOH in humans.

Justice Pentney identified three substantial gaps between the state of the art and the inventive concept:

1. The new formulation reduced the amount of bimatoprost from 0.03% to 0.01%. The prior art established that reducing the amount of bimatoprost would be expected to decrease efficacy in reducing IOP.
2. The new formulation drastically increased the amount of BAK from 50 ppm to 200 ppm. The prior art taught that BAK was cytotoxic and was known to cause ocular irritation and corneal damage at higher concentrations. The prior art taught away from using BAK or, at the very least, taught to use as little as possible.
3. The new formulation reduced the amount of bimatoprost and increased the amount of BAK to achieve greater or equal IOP reduction compared to old LUMIGAN. Though the prior art taught that BAK could potentially act as a penetration enhancer for some hydrophilic molecules, there was no indication that BAK would enhance penetration of a lipophilic compound like bimatoprost. There was no reason to believe that increasing BAK would set off the impact of reducing the amount of bimatoprost by enhancing penetration.

Justice Pentney held that it was not obvious to try to decrease the amount of bimatoprost and increase the amount of BAK to achieve greater or equal IOP reduction. The nature and degree of effort involved in reaching the invention was not routine or straightforward. The LUMIGAN team spent 2 and ½ years developing the new formulation, during which they tried several different approaches using 14 different formulations.

Insufficiency

Justice Pentney likewise held that the 691 Patent disclosed sufficient information to enable the skilled formulator to make the formulation in claim 16, and to enable the skilled ophthalmologist to administer it to patients with glaucoma and IOH.

Juno argued that the 691 Patent should be found invalid for insufficiency because:

1. The patent failed to disclose information which would allow the skilled person to draw meaningful inferences about the safety of the invention when administered to humans;
2. The patent failed to fully describe the advantage of 0.01% dose formulations to enable the skilled person to understand their benefits over old LUMIGAN;
3. The patent did not adequately disclose that 200 ppm BAK was used to increase ocular permeability of 0.01% bimatoprost; and
4. Since data based on rabbit studies cannot be directly extrapolated to humans, the Patent’s disclosure on permeability was insufficient.

Justice Pentney rejected each of these arguments in turn:

1. Allergan did not claim anything related to the safety profile of the new formulation, therefore failing to disclose this information was irrelevant. There was no evidence that the ingredients listed in claim 16 were so toxic to humans that they give rise to safety concerns.
2. The data in the Examples was sufficient to establish that the formulation in claim 16 would cause comparable or better IOP reduction compared to old LUMIGAN. The experts acknowledged that the Examples demonstrated superior ocular penetration achieved with either 0.03% or 0.015% bimatoprost and 200 ppm BAK as compared with old LUMIGAN. The Court accepted that ocular penetration was a proxy for IOP reduction.
3. The specification made it clear that the new bimatoprost formulation with 200 ppm BAK had the greatest permeability into the aqueous humour. A patent does not have to explain how the invention works so long as it explains how to work the invention.
4. While data based on rabbit studies cannot be expected to show precise results that will be achieved in humans, rabbit study data is regularly accepted as a basis for prediction regarding clinical results and it is sufficient to tell the skilled person what to expect from the new formulation. 

Justice Pentney concluded that the 691 Patent was not invalid for obviousness or insufficiency.

A copy of the decision is available here.