On March 31, 2012 Judge Sleet of the District Court for the District of Delaware concluded that the claims of four patents (7,410,978, 7,759,359, 7,781,448 and 7,781,449) asserted against Watson, Sandoz and Paddock were invalid for obviousness. The patents at issue, which derive from a common application, generally relate to once-a-day formulations of trospium for the treatment of over active bladder (OAB) and are listed on the Orange Book against Allergan’s SANCTURA XR product.
The decision is notable for its treatment of prior art in the field of pharmaceutical formulation, specifically the extent to which prior art disclosing extended release formulations of other active ingredients is relevant in the obviousness analysis of a once-a-day extended release trospium formulation.
Extended release dosage forms The Court began by noting that the asserted claims “do not cover a new drug, a new method of treatment, or novel ways of formulating trospium but were generally directed to pharmaceutical compositions that allow for once daily dosage forms of trospium. Trospium is a quaternary ammonium compound which, unlike other OAB drugs, is permanently positively charged. In various ways, the Plaintiffs sought to distinguish the prior art formulations on the basis they did not deal with extended release formulations of positively charged quaternary ammonium drugs, or on the basis that these references failed to discuss trospium’s “unique characteristics” and challenges. The Court did not accept these distinctions or the Plaintiffs’ submissions that this art “teaches nothing about once-daily trospium”. Rather, the Court concluded that the skilled person would find references teaching multiparticulate formulations for targeting drug release to the lower gastrointestinal tract relevant to developing a once-a-day trospium dosage form.
Trospium’s attributes The Court concluded that the skilled person would consider all of trospium’s attributes in determining whether it was a viable candidate for a once-a-day formulation. While acknowledging the evidence that trospium’s negligible colonic absorption made developing a once-a-day formulation more challenging than for other molecules, this negative attribute was insufficient to displace trospium’s positive pharmacological attributes, specifically its relatively long half-life, that favoured the development of a once-a-day formulation.
Motivation The Court relied on evidence that two other drugs for overactive bladder, tolterodine (DETROL) and oxybutynin (DITROBAN), were available as once-a-day formulations in 2002 and a reference disclosing that the overactive bladder market was moving towards once-a-day formulations as a motivation for the skilled person to develop a once-a-day trospium formulation.
Reasonable expectation of success / teaching away The Court did not accept that a poster reference disclosing that trospium has low rectal absorption taught away from the claimed invention and would have cause the skilled person to have a low expectation of success. Further, the skilled person would have questioned the methodology, results and reported conclusions of the reference. The Court also relied on evidence that the inventors’ employer, Shire, had developed multiple embodiments of the invention only two months after first receiving trospium.
Secondary considerations The Court did not accept that the Plaintiffs had demonstrated sufficient secondary considerations to refute a prima facie case of obviousness.
The Court also found (a) that the asserted claims were not anticipated; (b) claims 1 of the ‘978 and ‘449 patents were not indefinite; (c) claim 1 of the ‘359 does not lack written description. Assuming that the asserted claims were valid, the Court concluded that each of the ANDA applicants’ products directly infringe the ‘978 and ‘448 patents and indirectly infringe the ‘359 and ‘449 patents by inducement.
A copy of the Court’s memorandum may be found here.