By Nicholas Kaster, J.D.
The U.S. Court of Appeals for the Federal Circuit has affirmed a decision of the federal district court in Wilmington, Delaware, which held that patents awarded to pharmaceutical companies that invented a self-injectable testosterone replacement therapy drug marketed under the brand name Aveed were valid, and, therefore, an application filed by another pharmaceutical company for the production and marketing of a generic version of the drug would infringe on those patents. The Federal Circuit found no clear error in the district court’s conclusion that it would not have been obvious for a person having ordinary skill in the field to combine the prior art elements in the manner developed by the patent holder (Endo Pharmaceuticals Solutions, Inc. v. Custopharm Inc., July 13, 2018, Chen, R.).
Endo Pharmaceuticals Solutions Inc., Bayer Intellectual Property GmbH, and Bayer Pharma AG obtained two patents, U.S. Patent Nos. 7,718,640 (the 640 patent) and 8,338,395 (the 395 patent) (collectively, the patents-in-suit) for a composition formulated for the intramuscular injection in a single injection form that contains testosterone undecanoate (TU) as an active ingredient in a mixture of castor oil and benzyl benzoate. The FDA approved the drug, marketed as Aveed, as a testosterone replacement therapy for the treatment of male hypogonadism, a condition characterized by a deficiency or absence of endogenous testosterone. When Custopharm’s predecessor-in-interest, Paddock Laboratories, LLC, filed an Abbreviated New Drug Application (ANDA) in order to produce and market a generic version of Aveed, the patent holders filed an action against it alleging patent infringement. Custopharm argued that the patents-in-suit were invalid under the obviousness standard.
Under federal law (35 U.S.C. Sec. 103), a patent may not be obtained if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art. In this case, a trio of scientific articles served as a basis for establishing the prior art elements used in formulating testosterone replacement therapy drugs. The federal district court found that Custopharm had not met its burden of proving that the disputed claims would have been obvious. The court concluded that it was not obvious to a person having ordinary skill in the field to combine the prior art elements in the manner developed by the patent holder. The current appeal ensued.
The patents disclose three primary elements in the composition and administration of Aveed: (1) the testosterone dose (750 mg TU), (2) the vehicle formulation (a 40% castor oil and 60% benzyl benzoate vehicle), and (3) the injection schedule administered at an initial interval of two injections four weeks apart and maintenance injections at ten week intervals thereafter. Custopharm contended that the articles inherently describe the vehicle formulation and a skilled artisan would have recognized that patients were being overdosed with 1000 mg TU injections at a concentration of 250 mg/ml (for a total of 4 ml injected fluid). Relying on that premise, Custopharm argued that it would have been obvious to a skilled artisan to reduce the amount of injected fluid to 3 ml while maintaining the same TU concentration for a total of 750 mg TU per injection. This dose adjustment would in turn make the injection interval adjustment, including the use of a two-phase dosing regimen, obvious.
The Court of Appeals disagreed with each of these contentions, finding no clear error in the district court’s underlying factual findings.
On the testosterone dosage issue, the appeals court found that the lower court reasonably rejected Custopharm’s argument that a skilled artisan would consider 1000 mg of TU to be an overdose and would have been motivated to lower the dosage to the patented 750 mg. Furthermore, the district court found that Custopharm had not shown, by clear and convincing evidence, that a skilled artisan would have recognized that patients injected with 1000 mg TU were being overdosed. To meet its burden, Custopharm needed to do more than merely show that the prior art does not preclude lowering the dose of TU, the court said.
On the vehicle formulation issue, the court found that the prior art was replete with potential co-solvents 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. According to expert testimony, based on the articles’ disclosures, a skilled artisan would not have recognized that a co-solvent was necessary. And even if a skilled artisan concluded that a co-solvent was necessary, there were any number of available co-solvents.
Regarding the injection schedule, the appellate court noted that the articles, read together, do not clearly contemplate a two-phase dosing regimen with initial loading doses followed by maintenance doses. The articles themselves do not explicitly teach the use of loading doses. Thus, the Federal Circuit found that the district court did not err in considering the obviousness inquiry from the perspective of a skilled artisan confronted with the same problems as the inventor, which in this case was developing a commercially viable long-acting testosterone therapy. Doing so, the district court properly found that Custopharm failed to meet its burden of showing that a skilled artisan would combine the lowered dose with the injection schedule in the manner claimed.
Accordingly, the Federal Circuit affirmed the district court’s decision.
The case is No. 2017-1719.
Attorneys: Nevin M. Gewertz (Bartlit Beck Herman Palenchar & Scott LLP) for Endo Pharmaceuticals Solutions, Inc., Bayer Intellectual Property GmbH and Bayer Pharma AG. Douglass C. Hochstetler (Kelley Drye & Warren, LLP) for Custopharm Inc.
Companies: Bayer Intellectual Property GmbH; Bayer Pharma AG; Custopharm Inc.; Endo Pharmaceuticals Solutions, Inc.
MainStory: TopStory Patent FedCirNews
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