Frozen Liver Patent Tales

Evidently, human liver cells can be frozen several times and still “live.” I wouldn’t try this with steaks purchased from the grocery store (or your local butcher). The experts recommend one cryo-freeze only, for steaks. Interested in learning how this patented freezing technology works? Read on!

Celsis In Vitro, Inc. v. CellzDirect, Inc., No. 2010-1547 (Fed. Cir. Jan. 9, 2012) (Chief Judge Rader, Judges Gajarsa and Prost).

Frozen Livers

Celsis has a patent covering methods for preparing liver cells (called hepatocytes) that are capable of being frozen and thawed several times without significant reduction in the amount of live liver cells in the sample. This freeze-thaw cycle is called multi-cryopreservation.

Researchers use this method to preserve cells during investigations into the effect of compounds (that may be used to treat certain conditions or diseases) on drug candidates’ livers. Before multi-cryopreservation methods like this one, liver cells died quickly, even in a live liver (no pun intended). It was also hard to predict when these cells would be available for testing because they had to be harvested from donated livers.

Thus, the industry found significant value in the ability to freeze liver cells. With multi-cryopreservation, the cells could be transported longer distances from the donation location, multiple donation samples could be tested on demand, and samples harvested over a longer time period could now be tested together.

Stopping the Press

Celsis sued CellzDirect, Inc. and Invitrogen Corporation, now Life Technologies Corporation (LTC) for infringement of the patent. Soon after that, it asked the court to stop or enjoin LTC’s sales of its competing multi-cryopreserved liver cell product. After a month of discovery, the court held a hearing on the injunction request and granted it from the bench (during a hearing). LTC appealed that ruling.

On appeal, the Federal Circuit considered the four injunction factors: (1) likelihood of success on the merits, (2) irreparable harm, (3) balance of hardships, and (4) public interest. It also considered LTC’s invalidity defenses of noninfringement and obviousness.

As to infringement, the Federal Circuit considered the testimony of both parties “experts”—one is a scientist and the other is LTC’s marketing director. Both the trial court and Federal Circuit seemed to find Celsis’s expert testimony useful for tying the accused product to the patent claims. The trial court also found him more credible on the question of whether the accused product performs the claimed step of separating live and dead cells based on density.

Additionally, LTC argued on appeal that one patent step describing separation of the sample by density “without requiring a density gradient step” actually meant that a density gradient step would be prohibited in a product that met this claim. Since the accused product performs that density gradient step, it argued that LTC’s product does not infringe. The court concluded that this interpretation turned the language “without requiring” into “prohibiting”—an unnatural reading of the claim—and rejected this claim construction argument.

The court then turned to the obviousness issue. While numerous articles and testimony before the trial court discussed cryopreservation of liver cells, the district court noted that not a single one of them focused on the subject of multi-cryopreservation of hepatocytes. On appeal, LTC argued that an article by G. de Sousa filled this gap. The court disagreed, and concluded that the de Sousa article analyzes whether single-cryopreserved liver cells can replace fresh liver cells as laboratory models—not that it discloses multi-cryopreservation.

The district court also found LTC’s “revisionist history” unpersuasive. The Federal Circuit was similarly unmoved:

Not one of LTC’s experts testified to actually performing the claimed process or documenting their alleged understanding before the time of the invention, despite having the financial, scientific, and professional incentive to do so.

(See the opinion at pages 12-13.) The court also noted the unpredictability in this art area related to the ability to freeze liver cells even one time, much less multiple times.

Additionally, the court saw no error in the district court’s finding that Celsis would suffer irreparable harm absent a preliminary injunction. It agreed that price erosion, loss of goodwill, damage to reputation, and loss of business opportunities are all valid grounds for finding irreparable harm. It also ignored LTC’s new argument that these effects can be quantifiable in a two-competitor market and such harms are allegedly not irreparable in such a market. Since LTC chose not to properly raise this argument before the district court, the Federal Circuit declined the invitation to consider it for the first time.

Finally, the Federal Circuit affirmed the district court’s decision to grant Celsis a preliminary injunction.

Who’s Not on the Validity Train?

Judge Gajarsa dissented. He thought the district court’s obviousness analysis was legally deficient and that it used the incorrect clear and convincing standard of proof when analyzing the issue during the preliminary injunction stage. During a preliminary injunction effort, the district court must simply decide whether it is more likely than not that the patent will be proven invalid at trial, not whether there is clear and convincing evidence of its invalidity.

Judge Gajarsa also thought that the majority repeated these errors, and returned the obviousness standard to the time before the Supreme Court’s KSR decision. He stated that the majority required an explicit teaching, suggestion, or motivation for creating multi-cryopreserving liver cells in the prior art. In his mind, the multi-cryogenic preservation step would simply be obvious. If you freeze it once, you can freeze it again (unlike steak).

Here’s the Celsis opinion.