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

Case Name: Warner Chilcott Co., LLC v. Teva Pharms. USA, Inc., Civ. No. 11-6936 (FSH), 2015 U.S. Dist. LEXIS 26207 (D.N.J. Mar. 4, 2015) (Hochberg, J.) 

Drug Product and Patent(s)-in-Suit: Atelvia^® (risedronate / ethylene diamine tetraacetic acid); U.S. Pat. Nos. 7,645,459 (“the ’459 patent”), 7,645,460 (“the ’460 patent”), and 8,246,989 (“the ’989 patent”) 

Nature of the Case and Issue(s) Presented: Plaintiffs acquired the ’459 and ’460 patents when they purchased The Proctor & Gamble Company’s pharmaceutical division in August 2009. Those patents described a delayed-release formulation of risedronate in combination with ethylene diamine tetraacetic acid (“EDTA”), which is marketed as Atelvia. Atelvia is used to treat osteoporosis, and does not require that the patient be in a fasting state when the drug is administered. Typically, risedronate alone exhibits poor absorption when it is taken with food. This is due to the fact that calcium in food binds with the risedronate and forms a molecule that is too large for absorption in the small intestine. EDTA therefore is added as a chelating agent that binds with free calcium and prevents it from combining with risedronate, leaving a greater concentration of risedronate to be absorbed by the small intestines.

Prior to trial, Warner Chilcott agreed to drop all asserted claims related to the ’989 patent, and all claims of the ’459 and ’460 patents, except for claim 16 of the ’459 patent and claim 20 of the ’460 patent. Teva stipulated to infringement of those claims, and a bench trial was held to determine the issue of validity. The court found that those claims were invalid.

Why Teva Prevailed:  The court first considered Teva’s argument that a prior art reference known as the Brazilian Application anticipated the asserted claims. The Brazilian Application disclosed an enterically coated formulation containing a combination of a bisphosphonate and a chelating agent. It disclosed “methacrylic acid” as an acceptable enteric coating, and one that releases immediately “only in the small intestine.” It also disclosed risedronate sodium as an acceptable bisphosphonate and explicitly named the claimed ingredient disodium EDTA as an acceptable chelating agent. It disclosed use of an “effective quantity” of risedronate, which a person of ordinary skill would know included the most commonly prescribed and convenient dose: the claimed amount of 35 mg. And it disclosed a preferred range of disodium EDTA equivalent to between 20 and 175 mg, which includes the claimed amount of 100 mg. The literature did not teach away from using disodium EDTA, nor did it suggest using this amount of EDTA would be dangerous. It taught only that very high doses of EDTA were harmful and that using such very high doses of EDTA for the specific purpose of spreading the tight junctions was undesirable.

The Brazilian Application discussed two separate mechanisms to increase bisphosphonate absorption: (i) chelation, wherein EDTA binds to calcium molecules in food after a patient has eaten and blocks the calcium molecules from capturing the bisphosphonate; and (ii) permeability enhancement, wherein large doses of EDTA spread the cellular tight junctions, increasing overall intestinal absorption. As in the Brazilian Application, the challenged patents required “an amount of a chelating compound high enough to significantly bind the metal ions and minerals in food.” However, the challenged patents also require “an amount of a chelating compound…low enough not to significantly alter absorption of the bisphosphonate as compared to absorption in the fasted state.” Thus, the patents-in-suit chose one of the two methods set forth in the Brazilian Application. But the court found that there was insufficient evidence to clearly and convincingly find that any embodiment would necessarily produce the claimed element. The court held that the Teva did not meet its burden of proving that one practicing any disclosed embodiment of the Brazilian Application would inherently produce the claimed element of “pharmaceutically effective absorption,” and therefore the Brazilian Application did not anticipate either patent.

Concerning obviousness, the court found that there was clear and convincing evidence that a person of ordinary skill in 2005 would have been motivated to avoid the high levels of EDTA necessary to enhance permeability because the literature taught that such “extremely high” doses were undesirable. The court pointed to multiple prior-art references that explicitly suggested that chelating agents produced less variable bisphosphonate absorption after a meal. Additionally, the experts on both sides agreed that this disclosure informed a person of skill in the art that EDTA would block calcium after a meal, thus overcoming the food effect. The court cited an additional prior-art reference that was a strong predictor of success that EDTA could capture dietary calcium after a meal and allow an active ingredient to be absorbed without enhancing intestinal permeability. The court balanced this evidence of a known, desirable use for EDTA against the evidence that Atelvia met a need for an osteoporosis drug that lessened the consequence of failure to fast before administration. In light of all the circumstances, some satisfaction of a need was not sufficient to outweigh the extensive evidence in the prior art showing that coadministration of EDTA and a bisphosphonate would have the benefit of reducing the food effect. The court concluded that the plaintiffs’ evidence of secondary considerations did not tip the scales of patentability in its favor.