Ferring B.V. v. Watson Labs., Inc.

• Decision Date: 22 August 2014
• Docket Number: No. 2014–1416.,2014–1416.
• Citation: 764 F.3d 1401
• Parties: FERRING B.V., Plaintiff–Appellee, v. WATSON LABORATORIES, INC.-FLORIDA, Defendant–Appellant, and Apotex, Inc., and Apotex Corp., Defendants.
• Court: U.S. Court of Appeals — Federal Circuit

764 F.3d 1401

FERRING B.V., Plaintiff–Appellee,

v. WATSON LABORATORIES, INC.-FLORIDA, Defendant–Appellant,andApotex, Inc., and Apotex Corp., Defendants.

No. 2014–1416.

United States Court of Appeals, Federal Circuit.

Aug. 22, 2014.

Paul W. Browning, Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, of Washington, DC, argued for plaintiff-appellee. With him on the brief were James B. Monroe, Justin J. Hasford, and Mary E. Chlebowski.

B. Jefferson Boggs, Jr., Merchant & Gould P.C., of Alexandria, VA, argued for defendant-appellant. With him on the brief were Matthew L. Fedowitz; Christopher J. Sorenson and Rachel C. Hughey, of Minneapolis, MN.

Before LOURIE, DYK, and REYNA, Circuit Judges. LOURIE, Circuit Judge.

Watson Laboratories, Inc.—Florida (“Watson”) appeals from the decisions of the United States District Court for the District of Nevada (i) holding that the subject matter of the asserted claims of Ferring B.V.'s (“Ferring”) U.S. Patents 7,947,739 (the “'739 patent”), 8,022,106 (the “'106 patent”), and 8,273,795 (the “'795 patent”) would not have been obvious under 35 U.S.C. § 103, (ii) finding that Watson's generic tranexamic acid product infringed those claims under 35 U.S.C. § 271, consequently (iii) ordering the U.S. Food and Drug Administration (“FDA”) to reset the approval date of Watson's Abbreviated New Drug Application (“ANDA”) 20–2093 and (iv) permanently enjoining the manufacture, use, sale, or offer for sale of Watson's generic product. See Ferring B.V. v. Watson Labs., Inc.—Fla., No. 11–0481 (D.Nev. Apr. 14, 2014), ECF No. 524 (“ Final Order ”); J.A. 325–27. We conclude that the district court did not err in holding that the subject matter of the claims of Ferring's '739, '106, and '795 patents would not have been obvious. However, we conclude that the district court's judgment that Watson's generic product infringed the asserted claims of Ferring's patents was not in accordance with law. Accordingly, we affirm in part, reverse in part, and vacate both the district court's resetting order and injunction.

Background

Ferring owns the '739, '106, and '795 patents, which are directed to modified release formulations of trans–4–(aminomethyl)cyclohexanecarboxylic acid, also known as tranexamic acid, the active ingredient in the drug marketed as a treatment for heavy menstrual bleeding, or menorrhagia, under the brand name Lysteda®. The claims of those patents are drawn to oral dosage forms or formulations and methods of treating menorrhagia and require three elements: (1) about 650 mg of tranexamic acid; (2) a so-called modified release material that comprises either about 10% to about 35% or about 5% to about 50% by weight of the formulation; and (3) a specified dissolution release rate of the tranexamic acid in water as measured by a particular United States Pharmacopeia (“USP”) method. Claim 1 of the '739 patent is representative and reads as follows:

1. A tranexamic acid tablet formulation, comprising:

tranexamic acid or a pharmaceutically acceptable salt thereof; and a modified release material, wherein the modified release material comprises a polymer selected from the group consisting of hydroxyalkylcelluloses, alkylcelluloses, cellulose ethers, partial esters thereof, and mixtures thereof;

wherein the modified release material is present in the formulation in an amount from about 10% to about 35% by weight of the formulation;

wherein the formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by the USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37±0.5°C., of less than about 70% by weight tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes, and about 100% by weight tranexamic acid or pharmaceutically acceptable salt thereof released by about 120 minutes; and

wherein each tablet of the formulation provides a dose of about 650 mg of tranexamic acid.

'739 patent col. 69 ll. 46–67. Both claim 1 of the '106 patent and claim 1 of the '795 patent are similar but require a dissolution release rate of tranexamic acid of less than about 40% at about 15 minutes, less than about 70% at about 45 minutes, and not less than about 50% by about 90 minutes. '106 patent col. 69 ll. 8–19; '795 patent col. 35 ll. 37–48. Various dependent claims include additional limitations drawn to amount of tranexamic acid, amount or type of modified release material, water dissolution release rates measured by the USP test, pharmacokinetic requirements, and kind of dosage form. For example, claim 5 of the '739 patent and claim 19 of the '106 patent each limit the modified release material to hydroxypropylmethylcellulose, which is also known as hypromellose. '739 patent col. 70 ll. 20–22; '106 patent col. 70 ll. 62–64.

It is undisputed that the product Lysteda® is an embodiment of the claims in Ferring's '739, '106, and '795 patents. J.A. 938. Pursuant to the Hatch–Waxman Act, 21 U.S.C. § 355(b)(1), those patents are listed as referenced to Lysteda® in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations publication (commonly known as the “Orange Book”). In approving Lysteda®, the FDA recognized that the drug was intended for the treatment of a serious or life-threatening disease or condition that demonstrated the potential to address unmet medical needs. On that basis, the FDA granted the Lysteda® New Drug Application (“NDA”) “fast track” status under 21 U.S.C. § 356(b)(1), which provided for expedited review. J.A. 18449–63. Lysteda® is the first tranexamic drug approved by the FDA for treating menorrhagia in the United States.

Almost a year before the first of Ferring's patents issued, Watson filed ANDA 20–2093 seeking FDA approval to market tranexamic acid tablets as generic versions of Lysteda®. As specified in its ANDA, Watson's generic tablets are made of a so-called “core” mixture comprising 650 mg of tranexamic acid and various excipients including 6.52% by weight hypromellose, which is described as a binder. J.A. 13800.

Watson's initially-filed ANDA specified that the hardness of the cores was 13–20 kp; “kp” is an abbreviation for kiloponds, which is a measure of hardness compression. J.A. 13885. In an amendment submitted to the FDA dated August 29, 2012 and approved December 27, 2012, Watson modified its ANDA specification to require a core hardness of 13–17 kp. J.A. 13789, 13912, 13920. The cores are surrounded by a pH-dependent film coating comprising various agents including 1.86% Opadry® YS–1–7006, which itself is a mixture consisting of hypromellose and polyethylene glycol. J.A. 13800–02, 14074. The film coating is 2.91% by weight of the total weight of the composed tablet; it is designed to resist degradation in water, such as the mouth and the esophagus, but to dissolve immediately in acidic conditions, such as the stomach. Id.

Watson maintains that its ANDA contains no specification that addresses the manner in which its product dissolves in water. Appellant's Br. 24; J.A. 1598, 2080. However, biobatch data submitted in Watson's ANDA demonstrate that the dissolution release rate of tranexamic acid from its coated generic 650 mg tablets as measured by the USP 27 Apparatus Type II Paddle Method at 50 revolutions per minute in 900 mL of water at 37°C is as follows: 5% at 15 minutes, 16% at 45 minutes, 29% at 90 minutes, and 37% at 120 minutes. J.A. 14074.

In 2011, Watson submitted to Ferring a notice of certification pursuant to 21 U.S.C. § 355(j)(2)(B)(ii) and 21 C.F.R. § 314.95(c) regarding its proposed generic tranexamic acid product as specified in its ANDA. Ferring then initiated the instant suit, asserting that Watson's ANDA submission constituted an act of infringement of claims 1, 4, 5, 8–10, 12, and 13 of the '739 patent; claims 1, 5–8, 15, 16, 18, 19, and 30–37 of the '106 patent; and claims 1, 5, 6, and 8–10 of the '795 patent according to 35 U.S.C. § 271(e)(2)(A).^* Ferring alleged that both Watson's uncoated cores and finished, coated commercial tablets infringed the asserted patent claims. After receiving FDA approval of its ANDA on December 27, 2012, Watson launched its generic tranexamic acid product at risk, which Ferring did not move to enjoin. J.A. 14848–51.

During discovery, Ferring and Watson each conducted dissolution testing of samples provided by Watson. Of the hundreds of coated commercial products tested by the claimed USP method, only about four individual coated tablets released more than 50% of their tranexamic acid at 90 minutes, but none of them released more than about 79% by 120 minutes. J.A. 14218–76, 14751–53, 14768–69, 18290, 18424, 18427, 18443. The data collected by both parties showed that, in the majority of the samples tested, only about 27% to 44% of the tranexamic acid was released from the individual coated tablets at 90 minutes and only about 33% to 52% was released at 120 minutes, consistent with the biobatch data reported in Watson's ANDA itself. Id.

At trial, Ferring also relied on test data reported in a Watson document labeled PTX 381 to prove infringement. Appellee Br. 22; J.A. 991–93, 2003–11. Those data show dissolution profiles in water of experimental, uncoated 650 mg tranexamic acid cores of various specified hardness, as measured by the USP method, which Watson recorded in the development of its generic product formulation prior to submitting its ANDA to the FDA. J.A. 1617–19, 2070–72, 14840. The data show that the amount of tranexamic acid released in Watson's uncoated cores with a hardness of 13 kp is 96% at 15 minutes and 100% at 45 minutes; those with a hardness of 16 kp release 44% at 15 minutes and 95% at 45 minutes; those with a hardness of 17 kp release 27% at 15 minutes and 71% at 45 minutes; those with a hardness of 18 kp release 35% at 15 minutes and 76% at 45 minutes; and those with a hardness of 20 kp release 31% at 15 minutes and 77% at 45 minutes. J.A....