Warner Chilcott Co, LLC v. Teva Pharms. USA, Inc

Case Name:  Warner Chilcott Co, LLC v. Teva Pharms. USA, Inc., Nos. 2014-1439, 2014-1441, 2014-1444, 2014-1445, 2014-1446, 2014 U.S. App. LEXIS 21946 (Fed. Cir. Nov. 18, 2014) (Circuit Judges Lourie, Reyna and Taranto presiding; Opinion by Lourie, J.) (appeal from D. Del., Stark, J.) (The prior art and findings of the district court and Federal Circuit in a related action lead to a finding that the patents-in-suit were invalid as obvious.) 

Drug Product and Patent(s)-in-Suit: Actonel^® (risedronate sodium); U.S. Pats. Nos. 7,192,938 (“the ’938 patent”) and 7,718,634 (“the ’634 patent”) 

Nature of the Case and Issue(s) Presented:  The issue here concerns whether the district court was correct in granting summary judgment in favor of the defendants, finding that the asserted claims of the patents-in-suit were invalid due to obviousness. Risedronate salts belong to a class of compounds known as bisphosphonates, which bind strongly to bone mineral and are potent inhibitors of bone resorption. Daily oral dosing of bisphosphonates was known to cause irritation to mucous membranes and significant adverse esophageal and gastrointestinal side effects, which resulted in noncompliance of patients on the daily regimens.  The patents-in-suit claim a monthly dose of 150 mg of a bisphosphonate, among other infrequent dosing regimens, which is effective at treating osteoporosis.

From August 2008 through February 2011, various defendants submitted ANDAs to the FDA, seeking approval to engage in the commercial manufacture, use, or sale of generic versions of Actonel tablets.  Plaintiffs sued the defendants alleging infringement.

While the Actonel ANDA litigation was pending, the New Jersey District Court granted summary judgment of invalidity on the basis of obviousness in an ANDA litigation involving another bisphosphonate oral drug: ibandronate, dosed monthly at 150 mg and marketed by Roche under the Boniva^® brand name. The New Jersey court held that claims of the ’634 patent directed toward monthly oral administration of 150 mg of ibandronate were obvious. In the Delaware court, the defendants similarly moved for summary judgment of obviousness of the claims directed to monthly administration of 150 mg of risedronate. The Delaware court noted that several of the same pieces of prior art that were before the New Jersey court were currently before the Delaware court. After reviewing the cited prior art, expert declarations and evidence of secondary considerations, the Delaware court determined that the plaintiffs had failed to raise any issue of material fact and granted the defendants’ summary-judgment motion. The Federal Circuit affirmed.     

Why Teva Prevailed:  In order to prevail on appeal, defendants had to establish three limitations present in the cited prior art references: (i) oral administration of risedronate for the treatment of osteoporosis; (ii) once-monthly administration; and (iii) at a dose of 150 mg.

Plaintiffs argued that there was a genuine dispute of material fact as to whether a person of ordinary skill in the art (“POSA”) would have reasonably expected that dosing 150 mg of risedronate once monthly would be safe and effective. Plaintiffs also argued that there was a long-felt need for, and skepticism of others toward, the claimed monthly regimen. Lastly, plaintiffs argued that the Federal Circuit’s decision affirming the New Jersey court’s invalidity judgment in the related Boniva^® litigation should not be considered because ibandronate and risedronate are different compounds and the record in the instant case contained additional evidence of non-obviousness.

The Federal Circuit found that not only did the cited prior-art references disclose all of the claim limitations, but that the references also provided an express motivation to pursue the claimed monthly regimen and a reasonable expectation of success in doing so. Relying on a prior-art article stating that “risedronate ha[d] met all standards for efficacy and should receive FDA approval in the USA for prevention and treatment of osteoporosis in spring 2000,” the Federal Circuit found that defendants met element (i). That same prior-art article further stated that “[w]eekly, or even monthly, dosing if done properly could foster long term compliance as well as minimiz[e] side-effects,” thereby establishing point (ii). Another prior art reference cited by the defendants similarly stated that “[e]quivalent doses [of bisphosphonates] can be given every other day, twice a week, weekly, biweekly, or monthly.”

Additionally, the Federal Circuit found ample evidence in the record that using a monthly dose would be successful. One study cited by the defendants showed that “bisphosphonates were effective treatments for osteoporosis, even when dosed in intervals exceeding two weeks,” and that “risedronate…[wa]s effective in preventing bone loss even when given at long intervals.” A second study cited by the defendants established an increase in bone mineral density in patients treated with 30 mg of risedronate every day for 2 weeks, followed by a 10-week period of no treatment, and with that 12-week cycle repeated eight times over 2 years. The Federal Circuit noted that these studies provided express motivation to pursue a monthly dosing regimen.

The plaintiffs’ own expert testified that risedronate was known to exhibit a linear bioavailability from 2.5 mg to 50 mg, and that linear scaling of risedronate to a higher dose was merely unknown. The Federal Circuit did note that as of May 2002, the highest single dose of risedronate that had actually been tested in a patient was 50 mg. Despite this fact, the Federal Circuit concluded that obviousness does not require absolute certainty or a guarantee of success. Last, the Federal Circuit rejected testimony of plaintiffs’ experts that asserted that there was uncertainty regarding the safety and efficacy of a once-monthly regimen of 150 mg of risedronate. Again, the Federal Circuit stated that a lack of certainty does not preclude a conclusion of obviousness. The court rejected the plaintiffs’ remaining arguments and affirmed the district court’s determination that the asserted claims of the patents-in-suit were invalid due to obviousness.