O’MALLEY, CHEN, STOLL
August 10, 2016
Brief Summary: Board concluded that claims ‘250 1-20 relating to Teva’s 40 mg/ml glatiramer acetate (GA) product (Copaxone®) are unpatentable for obviousness.
Summary: This IPR relates to Yeda’s US 8,232,250, one of five patents expiring on Aug. 19, 2030 listed on the Orange Book for licensee Teva’s 40 mg/ml glatiramer acetate (GA) product (Copaxone®) for treating relapsing-remitting multiple sclerosis (RRMS) (no patents listed on the OB for the 20 mg/ml or 20 mg/vial products). Mylan filed an IPR seeking review of claims 1-20 of the ‘250 patent, which was granted on Aug. 25, 2015. Amneal had also filed an IPR regarding the same claims (IPR2015-01976) which was joined with IPR2015-00643. IPRs 2015-00644 and IPR2015-00830 (also requested by Mylan and Amneal) were also instituted against US 8,399,413 B2 and US 8,969,302 B2, respectively. Independent claims 1, 15 and 19 of the ‘250 patent relate to methods for alleviating symptoms of RRMS by administering “three subcutaneous injections of a 40 mg dose of glatiramer acetate over a period of seven days with at least one day between every subcutaneous injection”. IPR was instituted on obviousness grounds in view of two different sets of two references (Pinchasi and the 1996 SBOA, and Pinchasi and Fletcher). The Board determined that under the BRI, “the claims do not encompass an alternate-day administration schedule (i.e., one that administers the drug three times in one week and four times the next)” (ordinary meaning, Cuozzo (US 2016) and In re Translogic (FC 2007)) and corrected a typographical error in claim 3 regarding its dependency. It also agreed with Yeda that “a skilled artisan would have had knowledge of, and experience with, both MS and GA.” The Board was convinced that “Pinchasi teaches each limitation of claims 1 and 19, except for the requirement of three doses per seven-day period”, and concluded “that a person of ordinary skill in the art would have had a reason to modify the dosing regimen of 40 mg of GA every other day taught in Pinchasi to 40 mg of GA three times over a period of seven days” (e.g., crediting expert testimony that noted 40 mg and 20 mg showed “no significant difference in side effects”, and not being persuaded that a later phase III trial demonstrated less efficacy and “more frequent adverse effects”; no teaching away, In re Fulton (FC 2004) (“mere disclosure of more than one alternative does not constitute a teaching away”)). It also found the skilled artisan would have had a reasonable expectation of success, based in part on expert “testimony that an ordinary artisan would have considered GA to be a ‘forgiving drug’” and Teva’s patient instructions (“If you miss a dose, take your COPAXONE® as soon as your remember.”) It noted “the expectation of success need only be reasonable, not absolute” (Pfizer, FC 2007) and “[c]onclusive proof of efficacy is not necessary to show obviousness” (Hoffman-La Roche, FC 2014). The Board also found the other claims would have been obvious for similar reasons (e.g., skilled artisan “would have had a reason to switch patients treated with GA from dosing 20 mg daily to 40 mg three times over a period of seven days, and would have known that doing so would increase the tolerability of GA treatment”). It also found the alleged “surprising effectiveness and tolerability of” the 40 mg dosing regimen did not support nonobviousness (e.g., “Patent Owner has misinterpreted the data”). The Board did find a nexus between the 40 mg product and the claimed invention but also found the “Petitioner…presented sufficient evidence to rebut the presumed nexus”, thus the evidence of commercial success was found insufficient to support nonobviousness. And it found the Patent Owner had not presented sufficient evidence of long-felt, but unmet, need to support nonobviousness (“while there may have existed a long-felt needs, there also existed solutions to the problem”; differences between prior art and claimed invention are minimal (Geo. M. Martin, FC 2010). Thus, the Board concluded that Petitioner had shown by a preponderance of the evidence that claims ‘250 1-20 are unpatentable.