Decision: Cephalon, Inc. v. Slayback Pharma LLC, No. 1:17-cv-01154 (D. Del. April 27, 2020).

Holding: Judge Connolly in the District of Delaware decided that all of Cephalon's asserted claims are valid and infringed.

Patents: 9,265,831; 9,572,797; 9,144,568; 9,597,399; 9,572,887

Background: Cephalon sued ANDA filers for infringement of claims related to Bendeka®, a liquid formulation of bendamustine for treatment of chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Defendants unsuccessfully argued that the asserted formulation claims were invalid for obviousness, indefiniteness, lack of enablement and lack of written description. Defendants further unsuccessfully argued that the administration claims were invalid for obviousness.

The formulation claims recite non-aqueous liquid compositions containing at least the following elements:

1) bendamustine (or a pharmaceutically acceptable salt thereof);
2) about 5% to about 10% by volume of the solvent propylene glycol (PG);
3) the solvent polyethylene glycol (PEG);
4) one of the following ratios of PEG to PG: about 95:5, about 90:10, about 85:15, about 80:20, and about 75:25; and
5) a stabilizing amount of an antioxidant.

On non-obviousness, Judge Connolly found that defendants have established that a POSITA had reason to try to develop a non-aqueous, liquid, bendamustine formulations but not with PEG and PG as claimed. While he found that PG and PEG solvents would have been obvious to try based on the teachings of one reference, he found that a later reference taught away from using these solvents with bendamustine (due to degradation). Judge Connolly was persuaded by the later reference, which expressly discredited the earlier reference that also had not been relied upon to develop a formulation for decades. The court further found that the claimed PEG:PG ratios, while taught for use with another compound, would not have been obvious for bendamustine which degrades differently. Cephalon's objective evidence of commercial success (>$2 billion) was not found persuasive, but it was not necessary because His Honor found the Defendants did not show by "clear and convincing evidence that the prior art they cited would have motivated a POSITA to reach the claimed formulations." Id. at *31.

Administration claims recite methods of treating CLL or NHL with liquid bendamustine compositions at certain administration times and volumes. Certain claims require administering the bendamustine composition on certain days. One claim requires a bendamustine dose of "about 25 mg/m2 to about 120 mg/m2." And certain claims specify post-dilution bendamustine concentrations ranging from 0.05 mg/mL to 12.5 mg/mL. Judge Connolly found motivation for some of the claimed elements, he found none for others and that the claims, as a whole, were not shown to have been obvious.

Again, Cephalon's proffered objective evidence of nonobivousness, including skepticism, long-felt need, commercial success, and industry praise, were found not persuasive, but unnecessary in view of Judge Connolly's conclusion that Defendants had established neither a motivation nor a reasonable expectation of success for the claimed administration methods.

The Defendants raised § 112 arguments as well, including indefiniteness, enablement, and written description. In particular, the element "a stabilizing amount of antioxidant" was argued to be indefinite. However, Judge Connolly credited expert testimony "that a POSITA would know how to determine whether an amount of antioxidant is stabilizing." Id. at *58. Moreover, while Defendants argued that the specification does not explain how to determine whether stability has been increased, the court found that it provided a test method (HPLC) for measuring stability.

Defendants argued that the asserted formulation claims are "invalid for lack of enablement because the formulation patents disclosed neither the use of sodium hydroxide (NaOH) or of 'other undisclosed variables."" Id. at *61. According to Defendants, "a pH adjuster like NaOH is necessary to obtain the PG ester levels claimed in the [a]sserted [f]ormulation [c]laims." Id. Even though some claimed formulations did not result in the specified PG ester amounts, Judge Connolly found that undue experimentation was not required for a POSITA to obtain the claimed PG ester amounts and therefore rejected Defendants' argument that the claims were invalid for lack of enablement.

Defendants further argued that one claim was invalid for lack of written description, again relying on the "the absence of any mention of a pH adjuster like NaOH" and asserting this shows "that the inventors did not have possession of it at that time, as confirmed by their later filing of another patent application that discloses and claims it." Judge Connolly rejected this argument, however, noting that the Defendants "improperly cite[d] extrinsic evidence" rather than showing from the intrinsic record "that the asserted formulation patents claim something that they do not describe in their written descriptions." Id.

Take-Aways

This case makes clear, consistent with the Supreme Court's Graham opinion, that motivation to combine the asserted prior art references to reach merely some of the elements of the challenged patent claim is not enough. Lack of motivation to combine the asserted prior art references to reach the claimed subject matter, as a whole, is fatal as a matter of law to an obviousness challenge.

And kudos to those who wrote the specification and wrote and prosecuted the claims. Note the claims stood up to indefiniteness, written description, and enablement attacks.

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