Case Name: Bone Care Int'l, LLC v. Roxane Laboratories, Inc., Case No. 09-cv-285, 2012 U.S. Dist. LEXIS 80450 (D. Del. June 11, 2012) (Sleet, J.) (Medical professionals' educated judgments were sufficient for plaintiff to meet its burden on infringement; conversely, without a specific teaching in the prior art of the patented invention, defendants are not able to meet their heightened burden in proving obviousness.)
Drug Product and Patent(s)-in-Suit: Hectorol® (doxercalciferol); U.S. Patent No.5,602,116 ("the '116 patent")
Nature of the Case and Issue(s) Presented: Bone Care claimed that defendants' ANDA products infringed the '116 patent. In response, defendants claimed that the asserted claim was invalid as obvious. The district court construed the asserted claim at issue as having four limitations: (i) administering an amount of doxercalciferol; (ii) to patients with end-stage renal disease and secondary hyperparathyroidism; (iii) sufficient to lower and maintain lowered parathyroid hormone levels; (iv) with a lower incidence of hypercalcemia than would result from using calcitriol or alfacalcidol to achieve the same level of parathyroid hormone suppression. Bone Care asserts that defendants' ANDA products meet each and every element of the asserted claim. Defendants argue that plaintiffs have failed to prove infringement because doxercalciferol does not, in fact, result in a lower incidence of hypercalcemia than calcitriol or alfacalcidol, and their ANDA products do not meet claim element (iv) above. In support of this position, defendants take issue with Bone Care's expert testimony, rely on the Wesseling-Perry study, the only study to conduct a head-to-head comparison involving doxercalciferol and calcitriol or alfacalcidol, which found no differences in the incidences of hypercalcemia across these drugs, and the fact that the FDA did not allow Bone Care to include a superiority claim in its commercial labeling indicating that doxercalciferol is safer than calcitriol/alfacalcidol.
Defendants further argued that the asserted '116 claim was obvious. In particular, the defendants argued that it would have been obvious to use doxercalciferol to lower and maintain lowered serum parathyroid hormone in patients suffering from hyperparathyroidism and that one would obtain a lower incidence of hypercalcemia than would result from using calcitriol or alfacalcidol because doxercalciferol was known for almost ten years before the '116 patent's priority date. Bone Care responded that while doxercalciferol was known, a person of ordinary skill would not have expected the data and results that are disclosed in the '116 patent concerning the use of doxercalciferol. Bone Care further argued that the prior art teachings would cause a person of ordinary skill to do more research concerning doxercalciferol and its effect on serum parathyroid hormone in patients suffering from hyperparathyroidism and the incidence of hypercalcemia resulting from calcitriol or alfacalcidol.
Why Bone Care Prevailed: The Court found that defendants infringed the asserted claim of the '116 patent because there was sufficient evidence that treating with doxercalciferol had a lower incidence of hypercalcemia than would result from using calcitriol or alfacalcidol. While there was no direct, head-to-head study to compare the incidents of hypercalcemia resulting from administration of the drugs in question, medical professionals had a reasonable expectation that doxercalciferol would have a lower incident rate. The Court found Bone Care's expert testimony credible in that medical professionals do not wait for such comparisons, but make educated judgments of success based on known trial results. Thus, the Court found that Bone Care had provided sufficient evidence that doxercalciferol would have lower incident rate, and thus the accused products infringed the '116 patent.
As for invalidity, the Court found that defendants had not proven by clear and convincing evidence that the asserted claim was invalid under § 103. In particular, the Court focused on whether the prior art taught that using doxercalciferol would have a lower incidence of hypercalcemia than would result from using calcitriolor alfacalcidol. The Court found that defendants' arguments were based on impermissible hindsight. The prior art references that defendants relied on, according to the Court, would have only prompted one of skill to continue to investigate the treatment effects of doxercalciferol, not be in the possession of this invention. The prior art did not specifically teach or suggest that doxercalciferol would have a lower incidence of hypercalcemia than would result from using calcitriol or alfacalcidol, especially given that only one lab in the world has been doing research with doxercalciferol. In addition, the prior art references did not have any test results from human trials, and therefore, one of ordinary skill would have no expectation of results using doxercalciferol in humans. Thus, the Court found that the asserted claim of the '116 patent was valid.
