Board decision invalidating Sanofi’s Lantus®-related claims for obviousness affirmed

Sanofi-Aventis Deutschland GmbH v. Mylan Pharmaceuticals Inc.

Docket Nos. 2019-1368, -1369 (IPR2017-01526, -01528)
November 19, 2019

Brief Summary: Board IPR decision invalidating Sanofi’s Lantus®-related claims for obviousness affirmed.

Summary: Sanofi appealed USPTO (“Board”) IPR decision finding US 7,746,652 and 7,713,930 directed to insulin formulations comprising insulin glargine (“glargine”, “Gly(A21)-Arg(B31)-Arg(B32)-human insulin”) and a nonionic surfactant unpatentable for obviousness. The ‘652 and ‘930 patents are listed on the FDA Orange Book for Lantus® and Lantus® Solostar (NDA N021081; along with US 7,918,833 not at issue here). Exemplary claim 7 of the ‘652 patent claims “[a] pharmaceutical formulation” of glargine, “at least one chemical entity chosen from polysorbate and poloxamers”, “at least one preservative; and water”, and having a pH of from 1 to 6.8 (Lantus is described as having a pH of 4 and some zinc). The FC panel opinion explains that “[g]largine is a modified version of human insulin that, when injected as part of an acidic solution, acts for longer in a subject than does natural human insulin” and that a “vial-turbidity problem” due to “non-native aggregation” was resolved “by adding a nonionic surfactant”. Mylan’s IPR petition alleged obviousness in view of the Lantus® label and the non-patent prior art reference “Owens” and one of more of three secondary non-patent references (Lougheed, FASS, or Grau). The FC panel opinion explains that “[t]he main dispute is whether a relevant artisan would have been motivated to combine these references in the way claimed…with a reasonable expectation of success.” The Board found that motivation “based on a recognition that insulin had an aggregation problem in vials…and that surfactants (like the standard ones here) offered a solution” and that “Sanofi’s evidence of commercial success was too weak to support a conclusion of nonobviousness.” Sanofi argued to the FC panel that KSR required the Board to find “an aggregation problem for glargine specifically (not just insulins in general)” (KSR, US 2007; Randall Mfg., FC 2013), the Board relied on Sanofi’s specification to find the motivation (Panduit, FC 1985), and that “key evidence…concerned insulins in general rather than glargine specifically.” The FC panel first concluded that under KSR the Board properly examined the prior art’s recognition of “a potential aggregation-in-the-vial problem as part of the general recognition…with insulins” and “whether a relevant artisan would have recognized” it and “expected glargine to share that problem.” The FC panel also found no error with the Board’s reliance on Sanofi’s “background of the invention” section to support its “finding that insulin was known to aggregate on hydrophobic surfaces…in acidic solutions” (Smith&Nephew, FC 2013 (“used…for its teachings about prior-art knowledge”). And the FC panel found “the Board’s finding of a motivation to combine” to be “supported by substantial evidence” (In re Nuvasive, FC 2016 (“[t]he Board ‘must articulate a reason why a ‘[relevant artisan] would combine the prior art references”)) (e.g., “insulins ‘had a known tendency to aggregate’” including those “with a variety of amino acid structures”, “relevant artisan would have understood glargine to come within the general recognition”, nonionic surfactants known to address the problem”, unlike Novartis (FC 2015) in which rivastigmine had ‘greater chemical stability’ than physostigmine, reasonable expectation of success based on “success stabilizing other insulins and proteins”, expert testimony, evidence of commercial success unpersuasive (“hypothetical conjecture”, weakened by “Sanofi’s blocking patents” (Galderma, FC 2013; Acorda, FC 2018)). The Board’s decisions were therefore affirmed. Judge Newman dissented, arguing, e.g., that “neither the problem nor its remedy is shown in the prior art” (“hindsight analysis of foreseeability of the problem and its solution”), “[h]ere, the glargine was reformulated to preserve its stability, and achieved marked commercial success”, and that “Sanofi is entitled to the same benefit of the Arthrex decision as are the Arthrex parties.”

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

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