Tramadol hydrochloride 100 mg, 200 mg and 300 mg ER tablets (Ultram ER): Biovail Comments on Court Ruling

Innovator Biovail Corporation announced (in a press release Here ) that the United States District Court for the District of Delaware, Honorable Judge Kent A. Jordan has issued an opinion in favour of generic player Par Pharmaceuticals in the patent-infringement litigation relating to Tramadol hydrochloride 100mg and 200mg ER tablets (Ultram ER). Although Biovail is not a party to the action, the decision could have an effect on Biovail’s revenues relating to Tramadol hydrochloride 100 mg, 200 mg and 300 mg ER tablets (Ultram ER).

The following patents are listed in Orange Book for Tramadol hydrochloride 100 mg, 200 mg and 300 mg ER tablets (Ultram ER):

US6254887 (Assignee: Euro-Celtique S.A ; Expiry: May 10, 2014): The patent covers A controlled release oral pharmaceutical preparation suitable for dosing every 24 hours comprising a substrate comprising a pharmaceutically effective amount of tramadol or a salt thereof; said substrate coated with a controlled release coating; said preparation having a dissolution rate in vitro when measured using the Ph. Eur. Paddle Method at 100 rpm in 900 ml 0,1 N hydrochloric acid at 37.degree. C. and using UV detection at 270 nm, between 0 and 50% tramadol released after 1 hour; between 0 and 75% tramadol released after 2 hours; between 3 and 95% tramadol released after 4 hours; between 10 and 100% tramadol released after 8 hours; between 20 and 100% tramadol released after 12 hours; between 30 and 100% tramadol released after 16 hours; between 50 and 100% tramadol released after 24 hours; and greater than 80% tramadol released after 36 hours, by weight, said preparation providing a therapeutic effect for about 24 hours after oral administration.

US7074430 (Assignee: Euro-Celtique S.A ; Expiry: May 10, 2014): The patent covers a solid controlled release oral dosage form, comprising, a therapeutically effective amount of tramadol or a pharmaceutically acceptable salt thereof incorporated into a normal release matrix, said matrix overcoated with a controlled release coating comprising a polymethacrylate or a water insoluble cellulose, said dosage form providing a therapeutic effect for at least about 24 hours.

The holder of the patent Purdue Pharma (and partners like Biovail, Napp and ORTHO-McNEIL) were in litigation with generic player Par for this product in United States District Court for the District of Delaware since 2007.

The court opined that disputed claims 3, 13, 27 and 29 of ‘887 patent and claims 5, 7 and11 of ‘430 patents are infringed by Par’s generic product. However, the disputed claims are invalid and obvious in the light of Oshlak (US5580578) disclosure (alone) and Oshlak in combination with Kaiko (US5478577), Lintz and Stewart Leslie (one of the co-inventor of disputed patents) article entitled “Continues controlled release formulations”. The court further opined that the prior art clearly suggets that it would have been obvious for the formulator to develop controlled release formulation of the Tramadol with the use of excipients and formulation techniques available for person having ordinary skilled in the art. At the time of development of purdue’s formulation, the controlled release formulation of related compunds like Hydromorphone, Oxycodone, Dihydrocodeine, Codeine and Morphine were known. Also, controlled relese techniques and excipients were known as per Merck/Bondi patent EP147780. Importnatly, Judge concluded that the claimed invention is obvious both under pre KSR and Post KSR obviousness analysis.

Further, Judge rejected Par’s inequitable conduct charges (during prosecution of disputed patents with USPTO) against innovator Purdue and opined that patents is not invalid due to inequitable conduct.

The Court’s ruling, in conjunction with Par’s recent receipt of tentative approval from the U.S. Food and Drug Administration (FDA) for its 100mg and 200mg strength tablets, could allow Par to launch their generic formulation of those tablet strengths at any time. The generic player Par has not got final approval on 300 mg strength. Biovail will be consulting with its partner, Pricara (a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.) to determine next steps. The decision as to whether or not to appeal the decision lies with Purdue Pharma LP, the patent holder.

Biovail recorded Ultram® ER revenues of $81.9 million in 2008, and $37.2 million in the first half of 2009.

Update

Labopharm comments on judgment in Purdue patent litigation

Labopharm has commented on this litigation ( in a press release Here). In his decision, Circuit Judge Kent Jordan entered judgment in favor of Purdue and against Par on the issue of infringement and rejected Par's claim that the patents were unenforceable for inequitable conduct. Judge Jordan, however, entered judgment in favor of Par and against Purdue on the issue of validity, citing obviousness.

This judgment could permit Par to market its generic formulation of Ultram ER in the U.S., should it receive final regulatory approval from the U.S. Food and Drug Administration. Although Labopharm is not a party to this action, if Par was to launch its generic formulation of Ultram ER, it could impact U.S. sales of Labopharm's own once-daily tramadol product, Ryzolt(TM), which is marketed in the U.S. by Purdue. Ultram ER, and therefore any generic version of it, is not A/B rated to Ryzolt, meaning it cannot be substituted for Ryzolt at the pharmacy. Labopharm is currently in discussions with Purdue to evaluate next steps in this matter, including a potential appeal of the decision.