Moderna Therapeutics, Inc. et al. v. Arbutus Biopharma Corp.
Docket No. 2020-2329 (IPR2-19-00554) (https://cafc.uscourts.gov/opinions-orders/20-2329.OPINION.12-1-2021_1872458.pdf)
LOURIE, O’MALLEY, STOLL
December 1, 2021
Brief Summary: Board IPR decision of non-obviousness affirmed. Summary: Moderna appealed USPTO (“Board”) IPR holding the claims of US 8,058,069 directed to “nucleic acid-lipid particle[s]” for delivery of RNAi nucleic acids are not unpatentable as obvious. The claimed particles require nucleic acid, 50-65 mol % cationic lipid, 4-10 mol% (30-40 mol % of the total lipid) non-cationic lipid mixture of phospholipid and cholesterol (or a derivative thereof), and from 0.5-2 mol% “conjugated lipid that inhibits aggregation of particles”. In its IPR petition, Moderna argued the ‘069 claims would have been obvious over WO 2005/007196 (“the ‘196 PCT”) and US 2006/0134189 (“the ‘189 publication”) or ‘196 PCT, the ‘189 publication, “Lin”, and “Amad”; or, anticipated by or obvious over US 2006/0240554 (“the ‘554 publication”). The FC panel opinion explains that “Moderna’s arguments [were] based on the ‘196 PCT and ‘189 publication centered on alleged overlapping ranges of components” (e.g., ‘196 PCT discloses 2-60% mol % cationic lipid, 0.5-20 or 25% for the conjugated lipid, and 20-45 or 55% of the cholesterol portion of the non-cationic lipid). It explained that “[t]he parties’ dispute focused mainly on the phospholipid portion of the non-cationic lipid, for which the claims require a range “from 4 mol % to 10 mol % of the total lipid present in the particle” which Moderna acknowledged is not expressly disclosed by the prior art but “that, because the total mol % of all lipids in the particle must equal 100%, based on the ranges of the other lipid components, the maximum amount and minimum amount of phospholipid can be calculated to form a range of 0–19.5 mol %” and “the phospholipid range would have been obtainable through routine optimization using disclosed prior art formulations as starting points.” The Board disagreed, concluding that “a presumption of obviousness due to overlapping ranges did not apply in this case when ‘one of the claimed ranges for one of the expressly claimed sub-components of the claimed composition is not necessarily disclosed based on broader ranges for other components disclosed in the prior art’”, “Moderna failed to explain why a skilled artisan would have chosen those particular amounts” or “how or why a skilled artisan would have upwardly and downwardly adjusted the amounts of the components”, and “the evidence was ‘insufficient to establish that the claimed phospholipid range in particular was a recognized result-effective variable subject to routine optimization.’” The FC panel first explained that Moderna has demonstrated enough of a litigation risk to have Article III standing to appeal the Board’s decision (Grit Energy, FC 2020). On obviousness, the FC panel explained that it has “held that a presumption of obviousness typically exists ‘when the ranges of a claimed composition overlap the ranges disclosed in the prior art’” (In re Peterson, FC 2003), which is not the case here, and that Moderna’s argument that “it would have been a matter of simple subtraction for a person of ordinary skill in the art to derive a range for the phospholipid” is “an oversimplification based on unfounded assumptions” (e.g., the lipids “interact with each other unpredictably”). It also explained that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation” (In re Aller, CCPA 1955), “the parameter to be optimized must have been recognized by those skilled in the art to be a ‘result-effective variable’” (In re Antoine, CCPA 1977), and that ““[e]vidence that the variables interacted in an unpredictable or unexpected way could render the combination nonobvious” (App. Mat., FC 2012). And it found that Moderna failed to show “that reaching the claimed ranges for these result-effective variables would have been achievable through routine optimization” (e.g., it “failed to address the interdependence of the claimed lipid components and how adjustments would affect the nucleic acid-lipid particle as a whole”). Thus, the Board decision was affirmed.