Travoprost - USA

IPR decision (Sep 20, 2018):

AIA Review	Filing Date	Institution Date	Petitioner	Patent No.	Status
IPR2017-01053	03/10/2017	09/22/2017	Argentum Pharmaceuticals LLC	8,268,299	FINAL WRITTEN DECISION (Claims 1–28 are patentable)

On US’299 patent Apotex previously filed IPR (IPR2013-00428) on 07/05/2013 which was terminated.

US 8,268,299 (Alcon Research, Ltd.; Exp: Oct 13, 2029): OB listed

1. A multi-dose, self-preserved ophthalmic composition, comprising: zinc ions at a concentration of 0.04 to 0.4 mM; and borate and polyol, the borate being present in the composition at a concentration of 0.1 to 2.0% w/v and the polyol being present in the composition at a concentration of 0.25 to 2.5% w/v, the polyol comprising propylene glycol in the composition at a concentration of 0.25 to 1.25% w/v and sorbitol in the composition at a concentration of 0.05 to 0.5% w/v; wherein: (i) the composition has a concentration of anionic species less than 15 mM; and (ii) the composition exhibits sufficient antimicrobial activity to allow the composition to satisfy USP 27 preservative efficacy requirements.

22. A multi-dose, self-presened ophthalmic composition, comprising: an effective amount of travoprost; zinc ions at a concentration of 0.1 to 0.4 mM wherein the zinc ions are provided by zinc chloride; borate and polyol, the borate being present as boric acid in the composition at a concentration of 0.5 to 1.2% w/v and the polyol including propylene glycol and sorbitol, the propylene glycol being present in the composition at a concentration of 0.25 to 1.25% w/v and the sorbitol being present in the composition at a concentration of 0.05 to 0.5% w/v; and water; wherein: (i) the composition has a concentration of anionic species less than 10 mM; (ii) the composition exhibits sufficient antimicrobial activity to allow the composition to satisfy USP 27 preservative efficacy requirements; and (iii) the composition does not contain multivalent buffering anions and does not contain multivalent cations other than zinc.

26. A multi-dose, self-preserved ophthalmic composition, consisting of: an effective amount of travoprost; zinc ions at a concentration of 0.1 to 0.4 mM wherein the zinc ions are provided by zinc chloride; polyoxyl 40 hydrogenated castor oil; borate and polyol, the borate being present as boric acid in the composition at a concentration of 0.5 to 1.2% w/v and the polyol including propylene glycol and sorbitol, the propylene glycol being present in the composition at a concentration of 0.25 to 1.25% w/v and the sorbitol being present in the composition at a concentration of 0.05 to 0.5% w/v; sodium hydroxide and/or hydrochloric acid to adjust pH; and water; wherein: (i) the composition has a concentration of anionic species less than 10 mM; (ii) the composition exhibits sufficient antimicrobial activity to allow the composition to satisfy USP 27 preservative efficacy requirements; (iii) the composition does not contain multivalent buffering anions and does not contain multivalent cations other than zinc; and (iv) the composition has a pH from 5.5 to 5.9.

27. A multi-dose, self-preserved ophthalmic composition, consisting of: travoprost at a concentration of 0.004% w/v; ionized zinc chloride at a concentration of 0.0025% w/v; polyoxyl 40 hydrogenated castor oil at a concentration of 0.5% w/v; borate and polyol, the borate being present as boric acid in the composition at a concentration of 1.0% w/v and the polyol including propylene glycol and sorbitol, the propylene glycol being present in the composition at a concentration of 0.75% w/v and the sorbitol being present in the composition at a concentration of 0.25 w/v%; sodium hydroxide and/or hydrochloric acid to adjust pH; and water; Wherein: (i) the composition has a concentration of anionic species less than 5 mM; (ii) the e composition exhibits sufficient antimicrobial activity to allow the composition to satisfy USP 27 preservative efficacy requirements; (iii) the composition does not contain multivalent buffering anions and does not contain multivalent cations other than zinc; and (iv) the composition has a pH from 5.5 to 5.9.

28. A multi-dose, self-preserved ophthalmic composition, consisting of: travoprost at a concentration of 0.004% w/v; zinc chloride ionized in the composition at a concentration of 0.0025% w/v; polyoxyl 40 hydrogenated castor oil at a concentration of 0.5% w/v; and borate and polyol, the borate being present in the composition as boric acid at a concentration of 1.0% w/v and the polyol including propylene glycol and sorbitol, the propylene glycol being present in the composition at a concentration of 0.75% w/v and the sorbitol being present in the composition at a concentration of 0.25 w/v%; sodium hydroxide and/or hydrochloric acid to adjust pH; and water; wherein: (i) the composition has a concentration of anionic species less than 15 mM; and (ii) the composition exhibits sufficient antimicrobial activity to allow the composition to satisfy USP 27 preservative efficacy requirements.

PTAB’s conclusion: Petitioner asserts that an ordinarily skilled artisan “would have retained as much of prior art ‘Formulation A’ as feasible, as this was already an FDA-approved formulation, marketed as Travatan®.” But Petitioner’s challenge incongruously depends on at least six modifications to Formulation A; seven, if attaining UPS preservative efficacy requirements is not an inherent property of the modified composition. Petitioner does not address, much less explain, how or why an ordinarily skilled artisan, undertaking those six or seven modifications, would have done so with a reasonable expectation of success in arriving at a “self-preserved” composition using zinc as the sole preservative—in a field where zinc “had never before been the sole preservative in a marketed ophthalmic drug.” Formulation A bears almost no resemblance to the composition of claim 1, lacking three of the four required ingredients (zinc ions, sorbitol, and propylene glycol) and containing two others (BAC and EDTA) that are excluded by the “self-preserving” terms of the claim.

Thus, Petitioner has not shown by a preponderance of the evidence that claims 1–28 of the ’299 patent are unpatentable under 35 U.S.C. § 103(a).