“While Petitioner derives an overlapping phospholipid range by making certain assumptions about the other lipid components of the particle, nothing in Dupont, or any other Federal Circuit decision we are aware of, suggests that a presumption of obviousness applies under the circumstances presented here.” – PTAB Final Written Decision
On January 9, 2019, Moderna Therapeutics, Inc. (“Moderna”) filed a petition requesting inter partes review of U.S. Patent No. 8,058,069 (the ‘069 patent) owned by Arbutus Biopharma. The ‘069 patent is directed to lipid nanoparticle technology, the same technology that Moderna is using in its efforts to develop a vaccine for COVID-19. The Patent Trial and Appeal Board (PTAB) instituted review, but in their decision last week, determined that Moderna had not shown, by a preponderance of the evidence, that claims 1-22 of the ‘069 patent are unpatentable under 35 USC § 103.
The ‘069 Patent
The ‘069 patent is directed to stable nucleic acid-lipid particles (SNALP), methods of making them and methods of delivering them. Once so delivered, the nucleic acid portion of the SNALP may be used for therapeutic purposes such as RNA interference (RNAi). The ‘069 patent states that the disclosed SNALP provide “increased activity of the nucleic acid and improved tolerability of the formulations in vivo, resulting in a significant increase in the therapeutic index” as compared to similar prior art compositions. The ‘069 patent further asserts that the SNALPS described are stable in circulation and non-toxic to mammals.
The ‘069 patent discloses that the lipid portion of the SNALP generally comprises from 50 mol% to 85 mol% of a cationic lipid, from about 13 mol % to about 49.5 mol% of a non-cationic lipid, and from about 0.5 mol% to about 2 mol % of a lipid conjugate. A 1:57 SNALP, having 57 mol% ± 5 mol% cationic lipid, and a 1:62 SNALP having 62 mol% ± 5 mol% cationic lipid, are exemplified, with both having 1.5 mol% ± 0.5 mol% lipid conjugate, and the remainder made of up non-cationic lipid.
Claim 1 of the ‘069 patent is the sole independent claim of the ‘069 patent and in addition to a nucleic acid, recites from 50 mol % to 65 mol% of the cationic lipid, from 4 mol% to 10 mol % of the non-cationic lipid and from 0.5 mol% to 2 mol % of a conjugated lipid, all based on the total lipid present in the particle.
Moderna asserted that all claims of the ‘069 patent are either anticipated or rendered obvious by WO 2005/007196 to MacLachlan et. al. (“the ‘196 publication”) or U.S. 2006/0134189, also to MacLachlan (the ‘189 publication”) each taken alone, or taken together in combination with 2 NPL references to Lin and Ahmad, or, alternatively, anticipated or rendered obvious by U.S. 2006/02400554 to Chen (the ‘554 publication”).
As construed by the Board, the ‘196 publication discloses “using a small interfering RNA (siRNA) encapsulated in a serum stable lipid particle having a small diameter suitable for systemic delivery.” The ‘196 publication teaches a variety of ranges of cationic lipid – from 2% to about 60%, 5% to about 45%, 5% to 15%, or from 40% to 50% of the total lipid content. Suitable ranges for the non-cationic lipid are said to range from 5% to 90% or from 20% to 85% of the total lipid present, while the conjugated lipid is taught to suitably be present in amounts from 0.5% to about 50%, or from 0.5% to 25%, or from 1% to about 20%, or about 3% to about 15% or about 4% to 10% of the total lipid. The ‘189 publication was construed as disclosing very similar ranges.
Moderna argued that even though neither the ‘196 nor the ‘189 publication expressly disclosed a phospholipid within the ranges claimed in the ‘069 patent, that one of ordinary skill in the art would readily arrive at the claimed phospholipid amount by adjusting the amounts of the other lipid components and assigning the left over portion to phospholipid. Alternatively, Moderna argued that adjusting the amounts of various lipid components in the particle would have been a matter of routine optimization.
The Board Rejected Moderna’s Arguments
In order to anticipate, or render obvious, an overlapping range must be expressly taught.
Starting with the charge that either MacLachlan reference anticipated the ‘069 patent claims, the Board stated:
Petitioner does not point to any express disclosure of a phospholipid range in either the ‘196 or ‘189 publication. Petitioner, however, contends that “when combined with a cationic lipid proportion at the high end of the disclosed range (i.e., 60%), the available range for cholesterol is decreased to 20-40%,” and “the range for the other non-cationic lipid (e.g., a phospholipid) is also decreased to the portion not filled with cholesterol…namely 0% to 19.5%.
The Board further considered:
Here, the 5-90% range for non-cationic lipids generally disclosed in the ‘196 and ‘189 publications is considerably broader than the 4-10% range claimed specifically for phospholipids. Moreover, the references each disclose more preferred ranges for the non-cationic lipids that do not overlap with the claimed phospholipid range. Petitioner does not contend that the amount of phospholipid would not be considered critical to the claimed invention such that the broader prior art range may nonetheless anticipate the narrower claimed range. To the contrary, Petitioner acknowledges that having too much phospholipid ‘will inhibit release of the payload upon contact with the endosome.’…the evidence of record does not suggest the claimed nucleic acid-lipid particle would operate in the same manner if the phospholipid amount was adjusted across the entirety of the 5-90% range disclosed in the ‘196 and ‘189 publications.
And ultimately held:
We have considered the arguments and evidence presented and determine that Petitioner has not met its burden with respect to its Ground 1 challenges. In particular, we determine that the teachings of the ‘196 and ‘189 publications do not anticipate or otherwise render obvious a nucleic acid-lipid particle containing each of the recited lipid components with the claimed ranges, including specifically a phospholipid range of 4-10%.
The Board continued to explain why Moderna’s argument to modify the teachings of the ‘196 and ‘189 publications failed:
As stated above, neither the ‘196 nor the ‘189 publication explicitly discloses a phospholipid range. And while Petitioner derives an overlapping phospholipid range by making certain assumptions about the other lipid components of the particle, nothing in Dupont, or any other Federal Circuit decision we are aware of suggests that a presumption of obviousness applies under the circumstances presented here…To the contrary, the Federal Circuit has only applied the presumption where the overlapping range is expressly disclosed, not where an overlap might be assumed based on other motivating factors…even if a presumption could apply here, it is rebutted because we find nothing in the cited evidence indicating that the amount of phospholipid in a nucleic acid-lipid particle was recognized in the prior art as a results effective variable.
Support for this portion of the Board’s decision was said to be found in Ineos USA LLC v. Berry Plastics Corp., 783 F.3d 865, 869 (Fed. Cir. 2015) (“If the prior art discloses its own range, rather than a specific point, then the prior art is only anticipatory if it describes the claimed range with sufficient specificity such that a reasonable fact finder could conclude that there is no reasonable difference in how the invention operates over the ranges.”)
With respect to obviousness, the Board relied upon EI Dupont De Nemours & Co. v. Synvina C.V., 904, F.3d 996, which held that a presumption of obviousness based on overlapping ranges could be rebutted if the parameter requiring modification was not recognized as a result-effective variable.
‘Routine Optimization’ Must in Fact Be Routine
With respect to Moderna’s argument that routine optimization was all that separated the claims of the ‘069 patent from the prior art, the Board stated:
Even if a POSA would have been primarily motivated by a desire to improve transfection efficiency by increasing the amount of cationic lipid, Petitioner does not explain why that would have prompted the POSA to maintain the same amount of conjugated lipid and phospholipid as the 2:40 formulation, while decreasing the amount of cholesterol…Petitioner does not direct us to anything in the references suggesting that the 2:40 formulation would have been considered a more appropriate starting point for optimization than the 2:30 formulation. Thus, any further adjustments to the amounts of various lipid components in the 2:40 formulation in order to meet the claim requirement appears, on this record, to be hindsight driven.
The Board concluded that the ‘554 publication also did not include a teaching of the phospholipid range claimed, and rejected Moderna’s arguments based upon that reference using similar arguments. The Board thus held that Moderna had not established by a preponderance of the evidence that the claims of the ‘069 patent were anticipated or rendered obvious. As such, the Board did not address Arbutus’ objective indicia arguments and evidence.
Press After the Decision
Reuters reported the decision in a variety of outlets last week, noting that shares of Moderna had fallen nearly 10% after the decision was issued, while Arbutus shares more than doubled. The article also reported that, while Moderna can appeal the decision to the Federal Circuit, “that court…often upholds the patent office’s determinations.”
I’m not sure many practitioners – or the USPTO – would agree with that conclusion.