Apotex Inv. V. Wyeth LLC

Docket No. 2015-1871 (IPR2014-00115)

August 16, 2016


Brief Summary: PTAB final written decision of nonobviousness affirmed because “Apotex failed to explain why a skilled artisan ‘would have substituted tigecycline for minocycline’”.

Summary: Apotex appealed PTAB final written decision finding claims 1-23 of Wyeth’s (Pfizer’s) US 7,879,828 encompassing the antibiotic Tygacil® would not have been obvious. Representative claim 1 is directed to “[a] composition comprising tigecycline, lactose, and an acid selected from hydrochloric acid and gentisic acid, wherein the molar ration of tigecycline to lactose is between about 1:0.2 and about 1:5 and the pH of the composition in a solution is between about 3.0 and about 7.0.” The opinion explains that tigecycline degrades by oxidation at basic pH and by epimerization “[a]s the pH decreases” (“the epimer lacks the antibacterial efficacy of tigecycline”). The specification teaches that “the acid [of the claimed composition] minimizes oxidative degradation, and the carbohydrate [of the claimed composition] stabilizes the tigecycline against epimer formation at acidic pH.” IPR was instituted based on the combination of a Chinese patent application (“CN ‘550” (lyophilized tetracycline antibiotic (minocycline) with pH adjusting agent that can be lactose) and two non-patent references (“Pawelczyk” (addressing minocycline stability in a broad range of pHs (oxidation above pH 5)) and “Naggar” (rate of tetracycline epimerization, irreversible at pH 2-6, improved stabilization with solubilizers such as polysorbate 20, urea and thiourea)). The PTAB concluded in its final written decision, however, that “Apotex failed to explain why a skilled artisan ‘would have substituted tigecycline for minocycline in the CN ‘550 composition for any reason, much less in an attempt to make a lyophilized tigecycline composition that was stable against epimerization’” or “to combine [the three references], and use lactose, as a means for stabilization tigecycline against epimerization.” The FC opinion explained that the court reviews “the Board’s legal determinations de novo” (In re Elsner, FC 2004) and the “factual findings underlying those determinations” (e.g., what a reference teaches, reason to combine) “for substantial evidence” (In re Gartside, FC 2000). Apotex argued the Board improperly “imported an epimeric stability limitation into the claims, and thereby wrongly relied on the failure CN ‘550 to teach the epimeric stability of its composition” and “failed to consider any motivation to combine…beyond the problem the patentee was trying to solve, in contravention of KSR” (US 2007). The FC panel concluded the Board did not import epimeric stability into the claims but only considered it “during its obviousness analysis generally…in the context of assessing whether a skilled artisan would have been motivated to combine references.” It also concluded “the Board’s opinion” makes it “clear that it fully considered” other motivations (e.g., “tigecyline…was known to work where other antibiotics have failed”) as well as Apotex’s “unpersuasive” expert testimony. The FC opinion also stated that “there is not necessarily a motivation to substitute one antibiotic for a structurally related one when the prior-art antibiotic has a favorable stability profile, and there is nothing in the record here to show that the substitution would solve any other problem.” Apotex cited Senju (FC 2015) in its arguments, but FC panel explained that case “does not stand for the proposition that a skilled artisan would always be motivated to try later generation compounds in an old composition” but “turned on very specific factual findings”. It agreed with Apotex that “the Board did not expressly address” whether a skilled artisan would have been motivated to optimize the pH ranges in CN ‘550 or modified the same “because those ranges were commonly used in conventional injection solutions” but found “no reversible error in that omission in view of Apotex’s ultimate failure to establish why a skilled artisan would have been motivated to substitute tigecycline for minocycline, the dispositive issue here” (acknowledging “tigecylcine is closely related to minocycline structurally and in terms of benefit”). Thus, the Board decision was affirmed.

This entry was posted in Claim Construction, Generics / ANDA, Inter Parties Review (IPR), IPR, Obviousness. Bookmark the permalink.

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