The Federal Circuit Lays Out What Does and Does Not Meet the Standard of Inherency, Motivation to Combine and Burden of Proof in Challenging Validity of Issued Claims

July 20, 2018

      Endo Pharmaceuticals Solutions, Inc et al v. Custopharm, Inc. (Fed. Cir. July 13, 2018), is an appeal of a Delaware District Court rejecting Custopharm’s validity challenge to patents covering Endo’s Aveed® testosterone undecanoate (TU) intramuscular injection as part of a Paragraph IV ANDA filing.

      There were three core limitations in the challenged claims: (A) 750 mg testosterone undecanoate, (B) a vehicle mixture of castor oil and benzyl benzoate with certain concentration limitations, and (C) an administration interval. Custopharm relied on two basic theories of inherency and motivation to modify the prior art to modify the dosage and intervals.

      The Court correctly prefaced that the standard for inherency is “[t]he mere fact that a certain thing may result from a given set of circumstances is not sufficient.” (citations omitted). Custopharm relied on prior disclosure (“Articles”) of pharmacokinetic performance of the injectable but the Court was not persuaded:

First, Custopharm has not demonstrated that a skilled artisan could extrapolate the vehicle formulation used in the Articles from pharmacokinetic performance data. Custopharm’s own opening brief does not argue that the pharmacokinetic performance reported in the Articles can only be attributed to the claimed vehicle formulation.. .

Second, the prior art was replete with potential cosolvents such that a skilled artisan, reviewing the Articles, would not have necessarily recognized that the Articles’ authors used benzyl benzoate as a co-solvent for their reported clinical studies. . .

Custopharm’s argument falls short because it has not shown through any evidence why the pharmacokinetic performance profile reported in the Articles could be obtained only by using the claimed 40% castor oil/60% benzyl benzoate formulation.

      Custopharm’s alternative argument for obviousness was based on the use of a prior formulation called Proluton®:

Proluton was a commercially available, injectable steroid drug (hydroxy-progesterone) that used a vehicle consisting of approximately 40% castor oil and 60% benzyl benzoate. It was administered on a weekly basis at a concentration of 250 mg/ml to prevent miscarriages. Custopharm argues that, even though Proluton was administered weekly, a skilled artisan would have been motivated to use the vehicle formulation from Proluton to formulate a long-acting testosterone injection because hydroxylprogesterone and TU are both hormones injected at a high concentration of 250 mg/ml.

The Court was not persuaded because Custopharm failed to meet the required burden:

The district court correctly noted that it is Custopharm’s “burden to prove by clear and convincing evidence that a person of ordinary skill in the art would have been motivated to combine the Articles (and other cited prior art) with the vehicle used in Proluton.” . . .

[Proluton] is not a testosterone product for men; rather, it is administered to pregnant women to prevent miscarriage. And importantly, it is not an injectable . . not directed to prolonged activity.

      The Court continues along similar lines rejecting each of Custopharm’s alternative basis for obviousness because the “Articles” did not provide basis for the suppostions and Custopharm’s explanation was “lacking.”