June 2013
Motivation to Develop Drug Formulation Need Not Be Based on Rationale That Forms Basis for FDA Approval
| Judges: Dyk (concurring-in-part and dissenting-in-part), Prost (author), O’Malley |
| [Appealed from E.D. Tex., Judge Ward] |
In Allergan, Inc. v. Sandoz Inc., Nos. 11-1619, -1620, -1635, -1639 (Fed. Cir. May 1, 2013), the Federal Circuit reversed the district court’s finding that the claims of U.S. Patent No. 7,323,463 (“the ’463 patent”) were not invalid as obvious, and affirmed the district court’s finding that claim 4 of U.S. Patent No. 7,030,149 (“the ’149 patent”) would not have been obvious.
Allergan, Inc. (“Allergan”) is the holder of an NDA for a combination eye-drop product used for treating glaucoma comprising 0.2% brimonidine and 0.5% timolol, sold under the name Combigan®. Allergan holds four Orange Book-listed patents related to Combigan®: U.S. Patent Nos. 7,642,258 (“the ’258 patent”); 7,320,976 (“the ’976 patent”); 7,323,463 (“the ’463 patent”); and the ’149 patent.
Each of Sandoz, Inc., Alcon Laboratories, Inc., Alcon Research Ltd., Alcon, Inc., Falcon Pharmaceuticals, Ltd., Apotex Inc., Apotex Corp., and Watson Laboratories, Inc. (collectively “Sandoz”) filed an ANDA seeking approval to market a generic version of Combigan®. In response, Allergan sued Sandoz for infringing each and every claim of Allergan’s four Orange Book-listed patents for Combigan®.
Prior to trial, the district court granted SJ of noninfringement as to claims 1-3 of the ’149 patent. The parties stipulated to infringement of the other asserted claims. Therefore, the only issue tried in the district court was invalidity. After a bench trial, the district court found each of the asserted claims not invalid as obvious under 35 U.S.C. § 103. Sandoz appealed. Allergan attempted to cross-appeal the district court’s claim construction of claims 1-3 of the ’149 patent and the SJ of noninfringement. The Court, however, found the cross-appeal improper because there was no adverse judgment on the validity of claims 1-3 of the ’149 patent.
On appeal, the Federal Circuit first addressed whether the district court erred in finding the claims of the ’463 patent not invalid as obvious. The claims of the ’463 patent are directed to a composition comprising 0.2% brimonidine and 0.5% timolol, and Sandoz’s obviousness arguments relied upon an express motivation provided in the prior art to formulate fixed combinations of alpha2-agonists andbeta-blockers, including timolol, in order to increase potential compliance. The district court found that (1) there would be no motivation to create the fixed combination brimonidine/timolol product because the FDA did not view patient compliance as a factor for approval; (2) the formulation arts are unpredictable; (3) the prior art taught away from the claimed invention; and (4) there were secondary considerations that supported a finding of nonobviousness.
“There is no requirement in patent law that the person of ordinary skill [in the art] be motivated to develop the claimed invention based on a rationale that forms the basis for FDA approval. Motivation to combine may be found in many different places and forms; it cannot be limited to those reasons the FDA sees fit to consider in approving drug applications.” Slip op. at 9.
The Court found clear error in the district court’s conclusion that one of ordinary skill would not be motivated to develop a fixed combination brimonidine/timolol product with a reasonable expectation of success based on the prior art references. Noting that FDA approval may be relevant to the obviousness inquiry, the Court specified that “[t]here is no requirement in patent law that the person of ordinary skill [in the art] be motivated to develop the claimed invention based on a rationale that forms the basis for FDA approval. Motivation to combine may be found in many different places and forms; it cannot be limited to those reasons the FDA sees fit to consider in approving drug applications.” Slip op. at 9. Although the Court accepted the district court’s factual findings regarding teaching away and secondary considerations, the Court found that these factors were not enough to render the claimed invention nonobvious. Accordingly, the Court concluded that the claims of the ’463 patent were invalid as obvious.
Next, the Court addressed whether the district court erred in finding claim 4 of the ’149 patent not invalid as obvious. Claim 4 of the ’149 patent is directed to a method of reducing the number of doses of brimonidine without loss of efficacy by administering brimonidine in a fixed combination with timolol. The Court noted that the record firmly established that when brimonidine is dosed twice per day as opposed to three times per day, there is a loss of efficacy in the afternoon. But the Court found that “while it is true that the prior art shows concomitant administration of brimonidine and timolol was dosed twice per day, this art does not show that there was no loss of efficacy associated with that
treatment
. . . .” Id. at 14. Sandoz attempted to strengthen its obviousness argument by showing that, at the time of the invention, timolol had been combined with other ophthalmic drugs, though not
alpha2-agonists, to effectively treat glaucoma with a reduced number of doses. The Court, however, did not find any reason why the success of unrelated drugs would make it obvious to one of ordinary skill that a fixed combination of brimonidine and timolol could be dosed twice per day without loss of efficacy. Accordingly, the Court concluded that Sandoz failed to prove by clear and convincing evidence that claim 4 of the ’149 patent was invalid as obvious.
Finally, the Court addressed whether the district court erred in construing claims 1-3 of the ’149 patent. The district court construed the limitation of “the two compounds [brimonidine and timolol] are administered in separate compositions” to require that serial administration of brimonidine and timolol be compared to the fixed-combination product, whereas Allergan argued that the claims should be construed as comparing either drug individually to the combination product. Id. at 15-16. The Federal Circuit found no error in the district court’s claim construction.
Judge Dyk concurred-in-part and dissented-in-part. Judge Dyk joined in the majority’s holding that the claims of the ’463 patent were invalid as obvious, and that the district court correctly construed the relevant claims of the ’463 and ’149 patents. Judge Dyk disagreed, however, that claim 4 of the ’149 patent would not have been obvious. According to Judge Dyk, the majority found claim 4 of the ’149 patent not obvious because “it claims the result of twice-a-day dosing—avoiding ‘a loss of efficacy in the afternoon.’” Dyk Dissent at 3 (citation omitted). Judge Dyk noted that while a new and nonobvious method of using an existing composition may itself be patentable, a newly discovered result or property of an existing method of use is not patentable. In Judge Dyk’s view, “[a]voiding a ‘loss of efficacy’ is not a separate step, but rather a result of the claimed method.” Id.
