ModernaTx, Inc. v. Arbutus Biopharma Corp., No. 2020-2329, 2021 U.S. App. LEXIS 35472 (Fed. Cir. 2021)
Context: As part of its COVID-19 vaccine, Moderna has used a number of lipid particle technologies to encase and help deliver the mRNA vaccine payload into the body. Arbutus owns patents, including U.S. Patent 8,058,069 (the ‘069 patent), directed towards the lipid particle technology used by Moderna. Moderna thus brought the above case in anticipation that Arbutus would sue for infringement of the ‘069 patent.
Procedural History: Moderna first petitioned for an IPR of the ‘069 patent, asserting that the ‘069 patent is: 1) anticipated by or obvious over WO 2005/007196 (the ‘196 PCT), or US Pub. 2006/0134189 (the ‘189 publication); 2) obvious over a combination of the ‘196 PCT, the ‘189 publication, Lin[1], and Ahmad[2]; and 3) anticipated by or obvious over US Pub. 2006/0240554 (the ‘554 publication). PTAB found that Moderna failed to meet its burden. Moderna appealed.
Claim 1 of the ‘069 patent is the representative claim here (as the only independent claim). It reads:
1. A nucleic acid-lipid particle comprising:
(a) nucleic acid;
(b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid present in the particle;
(c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof, wherein the phospholipid comprises from 4 mol % to 10 mol % of the total lipid present in the particle and the cholesterol or derivative thereof comprises from 30 mol % to 40 mol % of the total lipid present in the particle; and
(d) a conjugated lipid that inhibits aggregation of particles comprising from 0.5 mol % to 2 mol % of the total lipid present in the particle.
As can be seen above, four different ranges are claimed in the patent as part of the lipid particle: 1) cationic lipid at 50-60 mol %; 2) phospholipid at 4-10 mol %; 3) cholesterol or derivative thereof at 30-40 mol %; and 4) conjugated lipid at 0.5-2 mol %.
Moderna argued in the IPR that the prior art references, particularly the ‘196 PCT and the ‘189 publication, taught ranges that overlap with three of the four ranges above, specifically the cationic lipid, the cholesterol or derivative thereof, and the conjugated lipid. Although the prior art was devoid of an express disclosure regarding the range of 4-10 mol % for the phospholipid, Moderna argued that such range could be inferred from the other ranges, or obtained through routine optimization, since the total amount of lipids must equal 100 mol %, and each of the ‘196 PCT and the ‘189 publication only taught using the same four components as in the ‘069 patent.
Moderna raised the interesting issue of whether a presumption of obviousness could apply where an overlapping range was not expressly taught in the prior art, and instead “assumed based on other motivating factors”. The Court had previously applied the presumption of obviousness only in cases involving ranges where the overlapping ranges were expressly taught in the prior art. However, the Federal Circuit held the door open for this issue by stating both that “[i]t is, however, also true that we have never affirmatively decided whether or not the presumption ever could apply in such a case” and “it is not necessary or appropriate for us to reach that general question [here]”.
Instead, the Federal Circuit held that Moderna was not able show that a person of ordinary skill in the art could have assumed/nevertheless understood a range for the phospholipid component that overlaps the range claimed in the ‘069 patent. Since Moderna could not satisfy the threshold showing that a person of ordinary skill in the art could fill in this missing range in the prior art, it was unnecessary to decide whether a presumption of obviousness was appropriate.
In particular, the Court agreed with PTAB that Moderna’s theory was “an oversimplification based on unfounded assumptions”. The Court indicated that Moderna had used a number of flawed assumptions, including that each lipid component could be freely adjusted across the entire disclosed range, and that one merely needed to decrease the percentage of another lipid component if one increased the percentage of a specific lipid component. Instead, the Court noted that the evidence in the case indicated that the components were instead interdependent and interacted with each other in unpredictable ways. This evidence of unpredictability was ultimately the factor that swayed the court in finding nonobviousness here, as there could be no routine optimization where the results were unpredictable.
There are two interesting takeaways from this decision. The first is that this decision by the Federal Circuit will likely lead to further litigation, given that Moderna appears to be infringing Arbutus’s ‘069 patent with their COVID vaccine formulation, and may potentially have further ramifications, given the substantial revenues involved with the vaccine sales. The second is that the Federal Circuit appears to be leaving the door open on whether a presumption of obviousness would be appropriate where a POSITA could fill in the blanks on a missing range for a component.
[1] Alison J. Lin, et al., Three-Dimensional Imaging of Lipid Gene-Carriers: Membrane Charge Density Controls Universal Transfection Behavior in Lamellar Cationic Liposome-DNA Complexes, 84 Biophysical J. 3307–16 (2003).
[2] Ayesha Ahmad, et al., New Multivalent Cationic Lipids Reveal Bell Curve for Transfection Efficiency Versus Membrane Charge Density: Lipid-DNA Complexes for Gene Delivery, 7 J. Gene Med. 739–48 (2005).