Simbrinza® (brinzolamide / brimonidine)
Case Name: Alcon Inc. v. Padagis Israel Pharms. Ltd., Civ. No. 22-1422-WCB, 2025 WL 457119 (D. Del. Feb. 5, 2025) (Bryson, C.J.)
Drug Product and Patent(s)-in-Suit: Simbrinza® (brinzolamide / brimonidine); U.S. Patents Nos. 9,044,484 (“the ’484 patent”) and 9,421,265 (“the ’265 patent”)
Nature of the Case and Issue(s) Presented: Simbrinza® is indicated for the treatment of heightened intraocular pressure associated with glaucoma. The patents-in-suit claim an ophthalmic composition containing: a first polyol, selected from mannitol, sorbitol, or a combination thereof (“mannitol”); a second polyol, selected from propylene glycol, glycerine, or a combination thereof; an effective amount of borate; a therapeutic agent; and benzalkonium chloride (“BAC”) as an anti-microbial preservative. BAC is a highly effective anti-microbial agent but is known to be harmful to the eye at higher concentrations. The claimed formulations render BAC an effective anti-microbial preservative even at low concentrations. At trial, the parties stipulated that the only limitation in dispute for the purpose of infringement was that which described a first polyol—mannitol—with a concentration between 0.01 w/v % and 0.5 w/v%. While both parties agreed that mannitol was not present in Padagis’ ANDA product, Alcon argued that Padagis’ use of tartrate (as brimonidine tartrate) at a concentration of 0.068 w/v% in the place of mannitol infringed this limitation under the doctrine of equivalents (the “DOE”). According to Alcon, DOE had to be applied independently to each element of this limitation. Padagis argued that DOE had to be applied to the limitation as a whole. The court agreed with Padagis and found that Padagis did not infringe the ’265 patent because tartrate at a concentration of 0.065 w/v% was not equivalent to mannitol at a concentration of between 0.01 w/v % and 0.5 w/v%. The Court also rejected Alcon’s argument that the differences between mannitol and tartrate were insignificant such that DOE should still apply under the “insubstantial differences” test.
Why Padagis Prevailed: When considering the level at which to apply DOE’s function-way-result test, the court noted that Alcon’s argument for an independent application to each element of the relevant limitation would effectively “erase a meaningful limit on the claim, i.e., that the claim covers the functionality of mannitol at concentrations within the range prescribed by the claim.” Specifically, the court noted that the concentration of mannitol described by the ’265 patent was not an independent limitation, but rather served to define the scope of the mannitol limitation itself. Because of the interdependence of these elements in defining the scope of this limitation, the court found that DOE had to be applied to the limitation as a whole.
The court went into considerable detail on the function and mechanism of action of mannitol and tartrate in each of the relevant ophthalmic compositions. While acknowledging much overlap in the functions these chemicals performed, the court ultimately found that they differed significantly in their ways of performing these functions and the results that they achieved. The court noted that mannitol had two purposes in the patented composition: first, improving the anti-microbial effect of BAC; and second, buffering the solution—and that it achieved these ends by complexing with borate via diols. The court found that tartrate, by contrast, had a much more limited buffering capacity, and complexed with borate through both carboxylic and hydroxyl groups, which resulted in different effects on the anti-microbial efficacy of BAC. Because of these differences in buffering capacity and because Alcon “did not prove that tartrate has the same anti-microbial effect as mannitol” at the relevant concentrations, the court concluded that Alcon had “not proved that the tartrate in Padagis’ ANDA product functions in substantially the same way or that it produces substantially the same results as the mannitol recited in the asserted claims.”
In support of its “insubstantial differences” test for applying DOE, Alcon cited to Padagis’ admission in its ANDA of bioequivalence. While acknowledging this test, the court rejected Alcon’s argument, noting that “bioequivalency and equivalent infringement are different inquiries. . . . Eequivalency for purposes of patent infringement requires an element-by-element comparison of the patent claim and the accused product, requiring not only equivalent function but also equivalent way and result.” Without further elaboration, the court rejected Alcon’s argument, holding that “Alcon’s theory of equivalence fares no better under the “insubstantial differences” test than under the “function-way-result” test.
