Exparel® (bupivacaine)
Case Name: Pacira Pharms., Inc. v. eVenus Pharms. Labs., Inc., Civ. No. 21-19829, 2024 WL 3812188 (D.N.J. Aug. 9, 2024) (Arleo, J.)
Drug Product and Patent(s)-in-Suit: Exparel® (bupivacaine); U.S. Patent No. 11,033,495 (“the ’495 patent”)
Nature of the Case and Issue(s) Presented: Exparel is a multivesicular liposome (“MVL”) drug product that acts as an analgesic for local pain relief. Exparel is an opioid alternative that is injected into a patient before surgery and provides sustained pain relief for three to five days, after which the patient can manage residual pain with a non-opioid medication. The ’495 patent describes a commercial scale manufacturing process for making bupivacaine MVLs with up to a five-fold increase in the final product volume. The claims of the ’495 patent recite a composition of bupivacaine MVLs having a target concentration from about 12.6 mg/mL to about 17.0 mg/mL wherein the erucic acid concentration in the composition is about 99 μg /mL or less after six months of storage. The court held a five-day bench trial and found that claim 7 of the ’495 Patent was invalid as obvious and anticipated in view of the prior art.
Why Defendants Prevailed: Obviousness. Defendants argued that the ’495 patent was obvious because the claimed erucic acid range was nearly identical to the range disclosed in the prior art. The court explained that it had to assess whether Defendants had satisfied their burden to show that the claimed erucic acid amounts were close enough to the amounts disclosed in the prior art, such that a POSA would have expected the same properties for both formulations. The court then had to weigh Plaintiffs’ evidence of: (i) critical range; (ii) teaching away; and (iii) secondary indicia of non-obviousness.
The six-month erucic acid concentrations disclosed by the prior art ranged from about 110 to 127 μg/mL. The court concluded that this was a de minimums difference to the claimed range given that Plaintiffs’ NDA stated that erucic acid concentrations up to 310 μg/mL would not affect product performance. As to critical range, Plaintiffs explained that the claimed erucic acid amount permitted longer shelf life and longer/more extreme temperature excursions. The court was unpersuaded, though, and concluded that there was insufficient evidence to show that the six-month erucic acid range was dissimilar to the range of erucic acid disclosed in the prior art. For teaching away, Plaintiffs argued that it was well known that MVLs are difficult to manufacture at a large scale while maintaining stability. The court agreed, but nevertheless found that this conclusion did not criticize, discredit, or otherwise discourage a POSA from arriving at the claimed invention. As to secondary indicia of non-obviousness, the court found no evidence of commercial success, as there was no testimony tying the claimed attribute, stability, to consumer demand. The court also concluded that the claimed invention did not satisfy a long-felt need. Indeed, while a need for a non-addictive analgesic arose after the opioid epidemic, this was not a need for the claimed invention: a larger-scale process for manufacturing stable MVLs.
Anticipation. Defendants argued that Plaintiffs’ prior-art formulation anticipated the ’495 patent. In support, Defendants averred that while the prior art did not explicitly practice the erucic acid limitation, it was inherently present. In response, Plaintiffs argued that non-prior art test batches—that allegedly had the same characteristics as the identified prior art—were not representative because they were made for regulatory purposes, not commercial sale, and that the processes for the two differed significantly. The court disagreed with Plaintiffs and concluded that the differences, if any, had no impact on the claimed limitations. Plaintiffs next argued that inherent anticipation must fail because at least one formulation in the prior art did not practice the six-month erucic acid limitation. The court disagreed with this argument and found that the ’495 patent was invalid for anticipation.
