Non-obviousness finding for Relistor® OB-listed formulation patent reversed due to structural and functional similarity to prior art compounds

Valeant Pharm. Int., Salix Pharm., Inc. et al. v. Mylan Pharm. Inc., et al., Actavis LLC

Docket No. 2018-2097
April 8, 2020

Brief Summary: DC grant of SJ of non-obviousness of OB formulation patent reversed and remanded based on structural and functional similarity of compound with prior art and failure to consider obvious-to-try evidence.

Summary: Mylan appealed DC grant of summary judgment (SJ) that claim 8 of Orange Book-listed (for Relistor®, one of eight OB-listed patents) Salix’s US 8,552,025 relating to stable methylnaltrexone preparations (“a pH between about 3.0 and about 4.0”, “stable to storage for 24 months at about room temperature”) is not invalid for obviousness. The FC panel reviewed the DC’s decision de novo (required by Third Circuit (NJ) law) to determine whether there is any “genuine dispute as to any material fact”, construing “the evidence in the light most favorable to the nonmovant” (FRCP 56(a); Anderson, US 1986). Mylan argued there was a motivation to “prepare and…arrive[] at the preparation of claim 8 via routine optimization of pH” (e.g., “obvious to try”) in view of US 5,866,154 (“Bahl”) for teaching stable naltrexone compositions with a pH of 3.0-3.5; US patent application (“Oshlack”) describing stable naltrexone compositions with an adjusted pH of “about 3 to about 5, but preferably to about 4”; a journal article (“Fawcett”) showing the stability of naltrexone “dwindled over time, and the pH of the formulations at all temperatures fell from 3.5 to 3.2”; and two treatises regarding the most useful pH for drugs (e.g., “with amide or ester linkages are prone to hydrolysis”). The DC disagreed with Mylan “because none of the references taught methylnaltrexone formulations”, “the evidence did not support that ‘adjusting pH would be the first variable formulators would consider to improve stability’”, and “that long-term stability of methylnaltrexone was a predictable result of arriving at a pH range of 3 to 4” (e.g., “a ‘large gap’ between [expert] testimony and the specified claimed pH range of 3 to 4 with its claimed stability profile of 24 months”). The FC panel explained that the DC focused “the remainder of its analysis” on “how the prior art references and expert testimony of record failed to establish” stabilization “based on pH alone” (e.g., neither Bahal nor Oshlack “taught a formulation ‘without added stabilizers’”; “the art did not contemplate an injectable solution ‘made stable over the long term by pH alone”). The FC panel agreed “with Mylan that the record supports a prima facie case of obviousness here” since “the pH range recited in claim 8 clearly overlaps with the pH range in the record art”, “these molecules bear significant structural and functional similarity”, and “prior art ranges for solutions of structurally and functionally similar compounds that overlap with a claimed range can establish a prima facie case of obviousness” (“When compounds share significant structural and functional similarity, those compounds are likely to share other properties, including optimal formulation for long-term stability.”; citing e.g., In re Peterson (FC 2003), In re Dillon (FC 1990) (“skilled artisans can expect structurally similar compounds to have similar properties”), In re Deuel (FC 1995) (“[s]tructural relationships may provide requisite motivation or suggestion to modify”); In re Merck, FC 1986 (close structural similarity and similar use); Anacor, FC 2018 (“compounds with common properties are likely to share other related properties as well”)). The FC panel did write that this “holding should not be misconstrued to mean that molecules with similar structure and similar function can always be expected to exhibit similar properties for formulation” (e.g., critical range, unexpected beneficial properties, teaching away (Geisler (FC 1997), Woodruff (CCPA 1990), Peterson). Thus, the FC panel found the grant of SJ to be an error.

The FC panel also agreed with Mylan that there were factual disputes precluding SJ (e.g., “disregarded Mylan’s obvious-to-try evidence because the pH ranges taught in the prior art were not sufficiently narrow”, “bounded range of pH 3 to 4 presents a finite number of narrower pH ranges for a skilled artisan to try” (KSR, US 2007), “no requirement that for a variable to be obvious to try, it must be the first variable a person of skill would alter”, “[a]bsolute predictability…not required”). Thus, the DC grant of SJ was reversed and remanded.

This entry was posted in Generics / ANDA, Obviousness, Obviousness (Secondary Considerations), Obviousness-Teaching Away, Summary Judgment. Bookmark the permalink.

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