Warner Chilcott Co. v. Teva Pharm. USA, Inc.

• Decision Date: 04 March 2015
• Docket Number: Civil Case No. 11–6936 FSH.
• Citation: 89 F.Supp.3d 641
• Parties: WARNER CHILCOTT COMPANY, LLC, et al., Plaintiffs, v. TEVA PHARMACEUTICALS USA, INC., Defendant.
• Court: U.S. District Court — District of New Jersey

89 F.Supp.3d 641

WARNER CHILCOTT COMPANY, LLC, et al., Plaintiffs

v.TEVA PHARMACEUTICALS USA, INC., Defendant.

Civil Case No. 11–6936 FSH.

United States District Court, D. New Jersey.

Signed March 4, 2015.

Cynthia Stencel Betz, Jonathan M.H. Short, William J. O'Shaughnessy, McCarter & English, LLP, Newark, NJ, for Plaintiffs.

Mayra Velez Tarantino, Michael E. Patunas, Lite Depalma Greenberg, LLC, Newark, NJ, for Defendant.

FINDING OF FACT AND CONCLUSIONS OF LAW

HOCHBERG, District Judge:

This Opinion constitutes the Court's findings of facts and conclusions of law pursuant to Federal Rule of Civil Procedure 52.

I. INTRODUCTION

Atelvia® —the osteoporosis drug covered by the challenged patents—purports to solve a problem experienced by patients who used earlier osteoporosis drugs: if the earlier drugs were taken with a meal, the active ingredient was captured by the calcium found in food molecules and was not absorbed into the body.¹ When the medicine failed to enter the bloodstream, patients' bones became susceptible to fractures. Atelvia® addressed this “food effect” by combining the active ingredient risedronate with a calcium-blocking agent, EDTA, thus permitting patients to take the drug with a meal and still receive an effective dose.

It is uncontested that prior art disclosed combinations of the active ingredient and the calcium-blocking agent EDTA to increase absorption. The closest reference—the Brazilian Application —disclosed two mechanisms to increase absorption: (1) a process called chelation, where EDTA binds to calcium molecules in food and blocks them from capturing the active ingredient; and (2) permeability enhancement, where large doses of EDTA spread the pathways between intestinal cells, allowing more active ingredient to pass from the intestine into the bloodstream.

By binding to calcium ions in food, chelation increases absorption only when a patient has eaten a meal; absorption of the active ingredient is thus similar regardless of whether a patient has eaten or not. On the other hand, permeability enhancement amplifies overall absorption of any intestinal content. Increased intestinal permeability was viewed as harmful because other drugs or bacteria could also more easily pass into the bloodstream.

Atelvia® employs only the first mechanism: it uses EDTA as a chelator to block the calcium in food, but not to enhance overall intestinal permeability. This achieves what the challenged patents call “pharmaceutically effective absorption,” a limitation defined as similar absorption whether a patient has eaten or fasted. Fed exposure within about 50% of fasting exposure is expected to be “pharmaceutically effective absorption.” Except for the “pharmaceutically effective absorption” limitation, the parties agree that the Brazilian Application contains “all of the elements of the asserted claim[s].” Thus, the main dispute is narrow: in light of the Brazilian Application's disclosure of EDTA's two mechanisms of absorption, whether it was obvious to modify the reference—using only the first disclosed mechanism of chelation and excluding the second disclosed mechanism of enhanced permeability—thus permitting a patient to take her osteoporosis medicine and receive a similar dose regardless of whether she has or has not eaten. In other words, was it obvious to use EDTA only as a calcium blocking agent to defeat the food effect, and would a skilled artisan have had a reasonable expectation of success in so doing?²

II. JURISDICTION

This Court has subject matter jurisdiction over this case pursuant to the patent laws of the United States and 28 U.S.C. §§ 1331, 1338, 1367, 2201 and 2202. Venue is proper in this District under 28 U.S.C. §§ 1391 and 1400(b). This Court has jurisdiction over the parties.

III. BACKGROUND

a. Procedural

Plaintiffs Warner Chilcott Co., LLC, and Warner Chilcott (US), LLC, (collectively “Plaintiffs” or “Warner”) bring this patent infringement action against Teva Pharmaceuticals USA, Inc., (“Teva”) under the Federal Food, Drug, and Cosmetics Act (“FFDCA”), and, more specifically, the Hatch–Waxman Amendments to that law. Plaintiffs assert that two patents protect Atelvia® from generic competition: U.S. Patent No. 7,645,459 (the “'459 patent”) and U.S. Patent No. 7,645,460 (the “'460 patent”). Both patents describe a delayed-release formulation of the active ingredient risedronate in combination with ethylene diamine tetraacetic acid (“EDTA”). Warner acquired these patents when it purchased The Proctor & Gamble Company's pharmaceutical division in August 2009. (Joint Stipulation of Facts ¶ 3, Dkt. No. 270). Plaintiffs hold an approved New Drug Application (“NDA”), No. 22–560, under § 505(a) of the FFDCA, 21 U.S.C. § 355(a), for a delayed-release risedronate tablet formulation containing 35 mg of risedronate sodium and 100 mg of disodium EDTA, and marketed as Atelvia®. (Joint Stipulation of Facts ¶¶ 5, 70, 71). These tablets were approved by the Federal Food and Drug Administration (“FDA”) on October 8, 2010, and are promoted for the treatment of osteoporosis. (Joint Stipulation of Facts ¶ 69). Warner listed the ' 459, '460 patents and U.S. Patent No. 8,246,989 in the FDA publication “Approved Drug Products with Therapeutic Equivalence Evaluations” (the “Orange Book”), in connection with Atelvia®. (Joint Stipulation of Facts ¶ 77).

As required by 21 U.S.C. § 355(j)(2)(A)(vii)(IV), Defendant Teva provided Plaintiffs with a “paragraph IV certification,” notifying Plaintiffs that they had submitted an Abbreviated New Drug Application (“ANDA”), No. 20–3217, to FDA seeking approval to manufacture and market generic versions of Atelvia® before the expiration of the '460 and '459 patents. Warner brought this patent infringement action against Teva within the forty-five day statutory period, filing a Complaint against the Defendant. Teva asserted counterclaims, seeking a finding that the challenged patents are invalid. Warner also filed patent infringement actions against the pharmaceutical companies Watson Laboratories, Ranbaxy, and Impax Laboratories, asserting these same patents. The Watson, Ranbaxy, and Impax actions were each resolved by settlement.

In its case against Teva, Warner has dropped all asserted claims of U.S. Patent No. 8,246,989, and all asserted claims of the '459 and '460 patents except for claim 16 of the '459 patent and claim 20 of the '460 patent. Teva has stipulated to infringement of these claims. (Joint Stipulation of Facts ¶ 40). A bench trial was held regarding the validity of claim 16 of the '459 patent and claim 20 of the '460 patent.

b. Technology At Issue

The challenged patents claim an active ingredient called risedronate sodium. This drug is a member of a class called bisphosphonates, which have been used for decades to treat osteoporosis. This active ingredient is combined with an inactive ingredient called disodium EDTA, which chelates—or binds—metal ions in food, blocking them from capturing the active ingredient when a patient has eaten.

1. Bisphosphonates

Bisphosphonates have been used since the 1980s to treat osteoporosis and Paget's disease. (Trial Tr. 1A.100:16–25).³ These diseases are characterized by a weakening of the bone. In a healthy human body, bone tissue is continually regenerated in an equilibrium of bone growth and bone disintegration. (Tr. 1A.103:14–104:9). Osteoblasts, a type of cell that builds new bone, are balanced by osteoclasts, a type of cell that destroys bone in a process called resorption. (Id.; Joint Stipulation of Facts ¶¶ 84, 85). In patients with osteoporosis, this normal balance is disrupted and bone resorption exceeds bone growth, leading to lower bone mass and a higher chance of fracture. (Tr. 1A.104:1–6).

Bisphosphonates have a strong affinity for the calcium crystals in bone, binding tightly to bone surfaces. (Tr. 1A.104:10–17). When a bone-destroying osteoclast engulfs a bone particle that is attached to a molecule of bisphosphonate, the osteoclast cell becomes less active or is destroyed. (Id.; PTX 135, at 176).⁴ Consequently, bisphosphonates inhibit bone resorption. (DTX 167, at 280). Over time, the administration of bisphosphonates results in less active bone-destroying osteoclasts, less resorption, and more bone tissue. (Tr. 1A.104:15–24). Many pharmaceutical companies have developed species of bisphosphonate for the treatment of osteoporosis. For instance, Warner marketed a 35 mg delayed-release risedronate tablet, called Actonel ®, which is the predecessor drug to the Atelvia® drug at issue. Warner held patents covering risedronate and Warner's Actonel® product, which expired on December 10, 2013. Merck developed an alendronate product, marketed as Fosamax ®; and Hoffmann–La Roche developed an ibandronate product, marketed as Boniva ®. (Joint Stipulation of Facts ¶¶ 42, 44, 57).

2. The “Food Effect”

Drugs that are administered by mouth travel from the mouth to the stomach, and then through the pylorus to the lower gastrointestinal tract—which includes the small and large intestine. (Joint Stipulation of Facts ¶¶ 88, 89). Bisphosphonate absorption occurs, to the largest extent, in the small intestine. (PTX 135, at 179). The small intestine consists of the duodenum, jejunum, and ileum. (DTX 234, at 589; Tr. 1A.106:3–6). There, the bisphosphonate passes from the intestines into the bloodstream.

There are two routes of transportation for molecules to pass from the intestine into the bloodstream: passing through the intestinal membrane cells themselves or passing through the spaces between the cells, called the tight junctions. (PTX 90, at 1744; Tr. 1A.107:1–8). Bisphosphonates do not pass through the membrane cells. Instead, they travel between the cells, through the tight junctions. (DTX 273, at 231; PTX 135, at 178–79; Tr. 1A.107:9–18). Once in the bloodstream, the bisphosphonate circulates; some is excreted and some is delivered to the bones, the site of the drug's action. (DTX 208, at 289; Tr. 1A.107:14–18).

Bisphosphonates are not...