Raloxifene Hydrochloride (Evista) 60 mg Tablets: District court upheld the validity of MOU patents; particle size patent declared invalid

Innovator Eli Lilly announced (in a press release Here ) that in a patent dispute with generic player Teva Pharma, the U.S. District Court for the Southern District of Indiana has upheld Eli Lilly and Company's method-of-use patents on Raloxifene Hydrochloride (Evista) 60 mg Tablets. The method of use patents provide patent protection for Raloxifene Hydrochloride (Evista) 60 mg tablets till March, 2014.

In addition, the Court held innovator Eli Lilly's Raloxifene Hydrochloride (Evista) 60 mg Tablets patents on particle-size, US6458811 (Expiry: Mar 10, 2017) and US6894064 (Expiry:Mar 10, 2017) as invalid. The court opined that generic player Teva has proved by clear and convincing grounds that the said patents are invalid due to lack of enablement under 35 USC 112. Further, court opined that description of the patent is not clear on partcle size evaluation in the formulations.

Background of patent litigation

Teva filed its Para IV certification against Following Orange Book listed patents

US5393763 (Expiry: Jul 28, 2012); which covers a method of inhibiting bone loss

US6906086 (Expiry: Jul 28, 2012); which covers a method of inhibiting post-menopausal bone loss in a post-menopausal woman in need of treatment to prevent or treat post-menopausal osteoporosis comprising administering a single daily oral dose to said woman of an effective amount of 6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl-4-[2-(piperidin-1-yl)ethox yphenyl]methanone hydrochloride.

USRE38968 (Expiry: Jul 28, 2012); which covers method of use in a post-menopausal woman in need of treatment to prevent or treat post-menopausal osteoporosis by use of Raloxifen

USRE39049 (Expiry: Jul 28, 2012); which covers method of use in a post-menopausal woman in need of treatment to prevent or treat post-menopausal osteoporosis by use of Raloxifen

USRE39050 (Expiry:Mar 2, 2014); which covers a method of inhibiting bone loss or resorption, or lowering serum cholesterol, comprising administering to a human in need thereof Raloxifen

US5478847 (Expiry:Mar 2, 2014); which covers a method of inhibiting bone loss or bone resorption comprising administering to a human in need thereof a Raloxifen, in an amount of about 50 to 150 mg/day.

US5457117 (Expiry: Jul 28, 2012); which covers a method of inhibiting bone loss comprising administering to a human in need thereof an effective amount of 6-hydroxy-2-(4-hydroxyphenyl)-benzo[B]thien-3-yl-4-[2-(piperidin-1-yl)etho xyphenyl]methanone hydrochloride.

US5393763 (Expiry: Jul 28, 2012); which covers a method of inhibiting bone loss or resorption, or lowering serum cholesterol, comprising administering to a human in need thereof Raloxifen

US5811120 (Expiry:Mar 2, 2014); which covers a solid administerable pharmaceutical formulation comprising raloxifene hydrochloride in combination with a surfactant, polyvinylpyrrolidone, and a water soluble diluent, wherein: the surfactant is a sorbitan fatty acid ester or a polyoxvethylene sorbitan fatty acid ester; and the water soluble diluent is a polyol or sugar.

US5972383 (Expiry:Mar 2, 2014); which covers a method of treating mammary tumors, prostatic tumors, or osteoporosis, comprising administering to a human in need thereof a solid orally administerable pharmaceutical formulation comprising raloxifene hydrochloride in combination with a surfactant, polyvinylpyrrolidone, and a water soluble diluent, wherein: the surfactant is a sorbitan fatty acid ester or a polyoxyethylene sorbitan fatty acid ester; and the water soluble diluent is a polyol or sugar.

US6894064 (Expiry:Mar 10, 2017); which covers a pharmaceutical composition comprising: a) 60 mg of 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]th iophene hydrochloride, characterized in that the benzo[b]thiophene compound is in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns; b) a surfactant; and c) a water-soluble diluent.

US6458811 (Expiry:Mar 10, 2017); which covers Raloxifen in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns.

US6797719 (Expiry:Mar 10, 2017): which covers Raloxifen in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns; b) a surfactant; and c) a water-soluble diluent.

Innovator sued Teva (within 45 days of Para IV notice from Teva) in Indiana Southern District Court in June, 2006 for infringement of method of use patents (Innovator not sued Teva on ‘064, '819 ,‘719 ), accordingly, Teva 's ANDA approval was delayed by 30 months.

Additionally, innovator also sued Teva for following patents not listed in Orange Book:

US5747510 (Expiry:Mar 2, 2014); A pharmaceutical formulation in daily dosage unit form comprising, per daily dosage unit, an amount within the range of about 55 to about 150 mg of Raloxifen or a pharmaceutically acceptable salt or solvate thereof, said formulation in dosage unit form being adapted for oral administration in the form of a capsule or tablet.

US5641790 (Expiry:Jun 24, 2014); A pharmacuetical formulation in dosage unit form comprising per dosage unit, an amount within the range of about 55 to about 150 mg of a Raloxifen or a pharmaceutically acceptable salt or solvate thereof.

The CAFC decision on ANDA approval of Teva Pharma:
Earlier, Innovator Eli Lilly got a favorable decision from Court of Appeal for federal Circuit (CAFC) on Feb 24, 2009 w.r.t Raloxifene Hydrochloride 60 mg Tablets. CAFC has delayed Teva’s ANDA approval by 6 months. The Chief Judge Rader and Michel affirmed a district court order (by 2-1, with dissent from fellow Judge Prost)) extending the thirty-month stay of USA approval of Teva's ANDA.
Court Opinion Here

Preliminary Injunction Opinion on “at risk launch” by Teva Pharma:
In April, 2009, innovator Eli Lilly announced (in a press release Here) that the U.S. District Court for the Southern District of Indiana has issued a preliminary injunction to prevent “at risk launch” of a generic version of Lilly's medicine Raloxifene Hydrochloride (Evista) 60 mg Tablets by Teva until the Court renders its final ruling. Earlier, Teva had indicated it was prepared to launch the generic version prior to the resolution of outstanding patent litigation currently being considered by the U.S. District Court for the Southern District of Indiana. Lilly had previously sought and been granted a temporary restraining order to prevent the generic launch.

Conclusion: Innovator succeded in establishing validity of method of use patents in District court, the said protection would be effective till 2014. In a partial viactory for generic player, Teva has been able to cut the patent protection of Raloxifene by almost 3 year. Also, both the parties can appeal against the said decision in higher court.