GlaxoSmithKline LLC v. Banner Pharmacaps, Inc.

Case Name: GlaxoSmithKline LLC v. Banner Pharmacaps, Inc., Civ. No. 11–0456–RGA, 2013 U.S. Dist. LEXIS 112440 (D. Del. Aug. 9, 2013) (Andrews, J.)

Drug Product and Patent(s)-in-Suit: Avodart^® (dutasteride); U.S. Patent No. 5,565,467 (“the ‘467 patent”)

Nature of the Case and Issue(s) Presented: The ’467 patent is directed at the synthetic drug compound dutasteride as well as the pharmaceutically acceptable solvates of dutasteride. Defendants stipulated to infringement, but contend that the ’467 patent is invalid due to the failure to meet the written description and enablement requirements, as well as due to the existence of intervening anticipatory prior art. Defendant Roxane also independently asserts that the ’467 patent lacks utility. The court held a bench trial and found that defendants did not prove any of the invalidity defenses by clear and convincing evidence.

Why Glaxo Prevailed: Defendants argue that although the ’467 patent claims all pharmaceutically acceptable solvates of dutasteride, it fails to disclose or enable all three solvate subgroups included in the court’s construction: crystalline, precipitated, and reacted. With regard to the written description requirement, defendants argue that the specification offers only conclusory statements that do not adequately describe all three solvates. But the court did not agree with the proposition that the specification must independently describe the three subgroups of the genus of pharmaceutically acceptable solvates. There is no reason why a person of ordinary skill in the art (“POSA”) would not credit a patentee with possession of a solvate merely because the patentee did not disclose solvates formed by each solvation process. Put another way, “whether it is said to be reacted, precipitated, or crystalized, a solvate is a solvate, and a solvate is detected when a [POSA] sees a complex of a solvent and a chemical compound.” The court further found that “dutasteride is where the novelty lies” and that the “concept of solvation, in contrast, has been known in the art for over 100 years.”

Moreover, all solvates of dutasteride retain the molecular structure and chemical function of dutasteride, and if those solvates were to arrive at the active sites, they would have the therapeutic effect. For the solvate to offer some therapeutic effect, it must be bioavailable. To achieve bioavailability, the solvate must be dissolved and have the requisite solubility in the body. Though the court ultimately rejected defendants’ written description defense, it credited defendants’ argument that bioavailability could not be predicted in advance of solvate formation; it found that bioavailability was determinable after the fact using x-ray refraction and other techniques to identify a solvate form.

As to the enablement, defendants argued that the claims of the ‘467 patent are broad and do not enable the full scope of “pharmaceutically acceptable” solvates, which requires more extensive and difficult enablement than solvates alone. The court addressed this issue in conjunction with factors that a court may consider when determining if a disclosure required undue experimentation, also known as the Wands (In re Wands, 858 F.2d 731 (Fed. Cir. 1988)) factors. Breadth of claims. Because solvates of organic compounds have long been known in the art, and the chemical compound of dutasteride is precisely claimed, this factor is neutral. The quantity of experimentation necessary and the state of the art. Glaxo had difficulty with the hydrated solvate of dutasteride when it attempted to commercialize its product, i.e., bulk form development. There was no evidence to suggest that Glaxo had those same issues when it sought to make a safe solvate with therapeutic effects. Additionally, any difficulties associated with the development of soft gel capsules and tablet formulation relates to the finished drug product, which need not be enabled by the patent. Finally, steroids were routinely ground up and dissolved in solutions to make solvates. Thus, this factor weighed in favor of enablement. Amount of direction and guidance in the ’467 patent. Although this factor was not briefed, there is an inference that the level of skill in the art is very high. “This means the person would have significant resources at his disposal and this factor favors finding the ’467 patent to be enabled.” Nature of the invention and predictability of the art. Because solvation has long been known in the art, steroids are prone to solvation, and methods of creating and testing solvates have also long been known, this factor weights slightly in favor of an enablement finding. Given the totality of the above findings, the court found that defendants have not met their burden in proving that the asserted claims were not enabled.

Defendants also argued that Merck formulated dutasteride before the priority date of the ’467 patent. They relied on a lab notebook of a Merck chemist, a compound data sheet, and an article co-authored by the same Merck chemist. While the documentary evidence illustrates that Merck knew of dutasteride and perhaps appreciated its significance, the court found that was not enough. Defendants, however, offered no inventor testimony in support of Merck’s independent conception of dutasteride. “The unexplained absence of the inventor’s testimony cannot and should not be ignored.” Defendants did not meet their burden because they did “not explain how Merck originally became aware of or interested in dutasteride and do not explain why no inventor testimony was offered. Further , the evidence indicates that Merck itself associated dutasteride, in one way or another, with [Glaxo].”

Lastly, Roxane’s lack of utility argument consists of two prongs: (i) Glaxo’s in vitro data alone are not sufficient to find dutasteride useful, and there is no reasonable correlation between the in vitroand in vivo activity of dutasteride; and (ii) nothing in the specification discloses that dutasteride is selective to the androgen receptor, and the lack of such selectivity would make a drug completely useless to a POSA. The court found that Roxane’s first argument would entail imposing an unjustified level of scrutiny to a patentee’s statements that were accepted as credible by the USPTO. Relying on Federal Circuit precedent, the Court found that results from animal tests or in vitro experiments may be sufficient to satisfy the utility requirement. In regards to Roxane’s second argument, the court found that a POSA would accept the fact that his class of steroids would not trigger the androgen receptor, and thus not cause the dangerous side effects, for the purposes of the utility analysis. “The lack of in vitro evidence on this point does not provide clear and convincing evidence of no utility where the activity at issue is a side effect reported in the art as generally not a factor with this particular class of drugs.”