Brimonidine & Timolol – USA

On Aug 29, 2019, Federal Circuit affirmed district court’s decision of patent validity & preliminary injunction in Combigan® case.

This appeal concerns Allergan’s patents, U.S. Patent Nos. 9,770,453, 9,907,801, and 9,907,802. The These patents share common specification & are related to combination of Brimonidine and Timolol for topical ophthalmic use. Sandoz filed ANDA with USFDA to market generic version of Combigan®. Allergan sued Sandoz under Hatch-Waxman regulation for infringement. New Jersey District Court found limiting a number of “wherein” clauses in these patents and granted Allergan’s motion for a preliminary injunction. Sandoz appealed.

Sole issue on appeal was with respect to the claim construction of clause, “wherein”. Sandoz argued that the wherein clause should be construed broadly because it is not limiting as it “merely state the intended results”. On the other side Allergan argued that the clause should be construed as limiting because “it is material to the patentability”.

Independent claim 1 of the ’453 patent is representative and recites:

 A  method of treating a patient with glaucoma or ocular hypertension comprising topically administering twice daily to an affected eye a single composition comprising 0.2% w/v brimonidine tartrate and 0.68% w/v timolol maleate, wherein the method is as effective as the administration of 0.2% w/v brimonidine tartrate monotherapy three times per day and wherein the method reduces the incidence of one o[r] more adverse events selected from the group consisting of conjunctival hyperemia, oral dryness, eye pruritus, allergic conjunctivitis, foreign body sensation, conjunctival folliculosis, and somnolence when compared to the administration of 0.2% w/v brimonidine tartrate monotherapy three times daily.

Federal Circuit said that wherein clause of claim 1 recites both efficacy & safety. It further said that though there is overlap between the language of the “wherein” clauses and those results, claims should be read in view of the “entire specification.”  The specification of the Patents-in-Suit demonstrates that the claimed invention is ultimately a formulation (and methods of using that formulation) that allows for increased efficacy and safety, i.e., a decreased risk of adverse events. Example II clinical study of the specification directly compares use of the Example I formulation with those prior art treatments and concludes that the claimed method is “superior” in both efficacy and safety. Thus, the specification demonstrates that Allergan believed the increased efficacy and safety of the claimed methods to be material to patentability. Allergan also relied on the efficacy and safety of the claimed methods during prosecution of the Patents-in-Suit in responding to the examiner’s rejections. Moreover, the Examiner explicitly relied on the “wherein” clauses in explaining why the claims of the Patents-in-Suit were “novel and non-obvious over the prior art.”

Therefore, in view of these strong intrinsic evidence, Federal Circuit sided with Allergan & held that the “wherein” clauses are material to patentability and thus limiting. Federal Circuit, thus found Sandoz’ arguments unpersuasive & held patents valid & affirmed injunction.