Merck & Co. v. Teva Pharmaceuticals Usa

• Decision Date: 28 January 2005
• Docket Number: No. 04-1005.,04-1005.
• Citation: 395 F.3d 1364
• Parties: MERCK & CO., INC., Plaintiff-Appellee, v. TEVA PHARMACEUTICALS USA, INC., Defendant-Appellant.
• Court: U.S. Court of Appeals — Federal Circuit

395 F.3d 1364

MERCK & CO., INC., Plaintiff-Appellee, v. TEVA PHARMACEUTICALS USA, INC., Defendant-Appellant.

No. 04-1005.

United States Court of Appeals, Federal Circuit.

Decided: January 28, 2005.

John F. Lynch, Howrey Simon Arnold & White, LLP, of Houston, Texas, argued for plaintiff-appellee. With him on the brief were Nicolas G. Barzoukas and Richard L. Stanley. Of counsel on the brief were Paul D. Matukaitis, Edward W. Murray and Gerard M. Devlin, Merck & Co., Inc., of Rahway, New Jersey.

James Galbraith, Kenyon & Kenyon, of New York, New York, argued for defendant-appellant. With him on the brief were Maria Luisa Palmese and William G. James, II.

Before RADER, GAJARSA, and PROST, Circuit Judges.

GAJARSA, Circuit Judge.

Teva Pharmaceuticals USA, Inc. ("Teva") appeals the final judgment of the United States District Court of Delaware, which, after a bench trial, found Merck & Co.'s ("Merck") U.S. Patent No. 5,994,329 (issued Nov. 30, 1999) ("the '329 patent") not invalid as anticipated or obvious. The district court further found the '329 patent to be enforceable, and the ' 329 patent claims 23 and 37 constructively infringed by Teva's Abbreviated New Drug Application ("ANDA") under 35 U.S.C. § 271(e)(2)(A) of the Hatch-Waxman Act. Merck & Co., Inc. v. Teva Pharms. USA, Inc., 288 F.Supp.2d 601 (D.Del.2003) ("Merck"); Merck & Co., Inc. v. Teva Pharms. USA, Inc., No. 01-CV-0048, Order (D.Del. Sept. 24, 2003) (Final Judgment Order Pursuant to Fed.R.Civ.P. 54(b)) ("Final Judgment Order").¹

We disagree with the district court's construction of the claim term "about" in claims 23 and 37 of the '329 patent. Because we further hold claims 23 and 37 obvious in light of the prior art, we vacate the judgment of the district court and hold the claims invalid and not infringed.

I. BACKGROUND

A. '329 Patent

Merck owns the '329 patent. The '329 patent, entitled "Method for Inhibiting Bone Resorption," teaches a method of treating and preventing osteoporosis through less-than-daily administration of bisphosphonate compounds. '329 patent, col. 1, ll. 15-25. The patent was filed on August 14, 1998, and Merck stipulated at trial that it would not allege an invention date prior to July 22, 1997 for the claims at issue. Merck, 288 F.Supp.2d at 606.

Bisphosphonates are a family of chemical compounds that are known to selectively inhibit the bone destruction process that contributes to osteoporosis and other bone diseases. '329 patent, col. 1, ll. 45-50. Bisphosphonates include, among other compounds, alendronate, risedronate, tiludronate, pamidronate, ibandronate, zolendronate, and etidronate. Id. at col. 1, ll. 54-65; col. 2, ll. 28-31. At issue in this case are once-weekly dosages of alendronate monosodium trihydrate.

Bisphosphonates are not readily absorbed by the gastrointestinal ("GI") tract. The medications thus require rigorous dosing instructions: a patient must take the medicine on an empty stomach and remain upright and fasting for thirty minutes after ingestion. '329 patent, col. 2, ll. 3-24. In addition, the compounds are known to have adverse GI side effects that physicians believed to be related, in part, to (a) irritation to the patient's esophagus, or (b) the size of the dose. Id. at col. 2, ll. 23-46.

Before the '329 patent issued, standard osteoporosis treatments consisted of small daily doses of bisphosphonates to avoid GI complications. Id. at col. 1, ll. 54-61; col. 2, ll. 34-35, 44-46. According to the patent, however, the adverse GI side-effects resulting from repetitive irritation to the GI tract were the primary concern in the field. Id. at col. 2, ll. 65-67; col. 3, l. 57 — col. 4, l. 13. The inventors trumpeted the reduced-frequency dosing schedule disclosed in the '329 patent as decreasing the irritating effect of the compounds, as well as increasing patient compliance with the rigorous dosing instructions. Id. at col. 3, ll. 57-64; col. 4, ll. 14-23.

This case involves dependent claims 23 and 37 of the '329 patent. At trial, the parties agreed to cast the text of these claims in independent form, incorporating all the dependent limitations:

23. A method for treating osteoporosis in human comprising orally administering about 70 mg of alendronate monosodium trihydrate, on an alendronic acid basis, as a unit dosage according to a continuous schedule having a dosing interval of once-weekly.

37. A method for preventing osteoporosis in human comprising orally administering about 35 mg of alendronate monosodium trihydrate, on an alendronic acid basis, as a unit dosage according to a continuous schedule having a dosing interval of once-weekly.

'329 patent, col. 21, ll. 24-27 (claim 23) (emphasis added); col. 22, ll. 24-26 (claim 37) (emphasis added). We note that the only differences between claim 23 and claim 37 are (1) the dosage amount of alendronate monosodium trihydrate (70 mg or 35 mg) and (2) whether the method is directed to treating or preventing osteoporosis.

Merck has Food and Drug Administration ("FDA") approval to market both a once-weekly and a relatively diminished daily dose of alendronate monosodium trihydrate, which it does under the trade name Fosamax. Merck, 288 F.Supp.2d at 605.

B. Litigation

In late 2000, Teva amended an existing ANDA and sought FDA approval to market generic versions of Merck's once-weekly Fosamax supplement in 35 mg and 70 mg quantities.² Merck, 288 F.Supp.2d at 605-06; Teva Br. at 4. Merck subsequently filed suit against Teva under 35 U.S.C. § 271(e)(2)(A), alleging Teva's ANDA filing was an act of infringement.³

According to the trial court, Merck acted as its own lexicographer and through the specification redefined the ordinary meaning of "about" in claims 23 and 37 — which both parties agree has the ordinary meaning "approximately" — to something quite different. Merck, 288 F.Supp.2d at 612-16. Thus, the district court concluded the terms "about 35 mg" in claim 37 and "about 70 mg" in claim 23 mean exactly 35 (or 70) mg of alendronic acid.⁴

Relying on this construction of "about," the district court dismissed Teva's allegations that the claims at issue were (1) anticipated by a July 1996 Lunar News article or (2) rendered obvious by an April 1996 Lunar News article combined with the July 1996 article.⁵ The trial court found both articles qualified as prior art publications under 35 U.S.C. § 102(a). Merck, 288 F.Supp.2d at 618-19. The April 1996 article in Lunar News recommends weekly dosages of alendronate to improve patient compliance:

[O]ne of the difficulties with alendronate is its low oral bioavailability. When taken with water in a fasting state, only about 0.8% of the oral dose is bioavailable. Even coffee or juice reduces this by 60%, and a meal reduces it by >85%. Alendronate must be taken, after an overnight fast, 30-60 minutes before breakfast. Subjects should remain seated or standing; a very small group of patients have reported some upper gastrointestinal distress if this is not done. This regime may be difficult for the elderly [to] maintain chronically. An intermittent treatment program (for example, once per week, or one week every three months), with higher oral dosing, needs to be tested.

Update: Bisphosphonate, Lunar News, Apr. 1996, at 31 (emphasis added).

The July 1996 Lunar News article further emphasizes the need for a once-weekly dose of Fosamax because "[s]ome United States physicians are reluctant to treat [patients with Fosamax] because of: a) side effects; b) difficulty of dosing; and c) high costs ($700/year)." The author suggests:

The difficulties with oral bisphosphonates may favor their episodic (once/week) or cyclical (one week each month) administration. Even oral alendronate potentially could be given in a 40 or 80 mg dose once/week to avoid dosing problems and reduce costs.⁶

Update: Bisphosphonate, Lunar News, July 1996, at 23 (emphasis added).

Regarding anticipation, the trial court held the July 1996 article does not "expressly or inherently disclose the dosage amounts for alendronate in claims 23 and 37" because there was no evidence that 40 mg and 80 mg of alendronate contains "the same number of alendronate core molecules" as found in 35 mg and 70 mg, respectively, of alendronic acid. Merck, 288 F.Supp.2d at 618-20.

As for obviousness, the district court concluded the suggestion of weekly treatment was not "clinically useful or obvious in July 1997 because of the known dose-related gastrointestinal side effects" associated with the daily formulation of Fosamax. Merck, 288 F.Supp.2d at 628. Although it is undisputed that a once-weekly dosage was known to be efficacious, the court determined that the Lunar News articles could not overcome doctors' concerns associated with higher dosages because the Lunar News articles were not published in peer-reviewed journals or authored by one skilled in the art. Merck, 288 F.Supp.2d at 628-29.

Finding the '329 patent not invalid as anticipated or obvious, the district court delayed the effective date of the FDA approval of Teva's ANDA until the '329 patent expires and enjoined commercial sale of Teva's generic treatment. Final Judgment Order at 1. This appeal followed. We have jurisdiction under 28 U.S.C. § 1295(a)(1).

II. DISCUSSION

A. Standard of Review

On appeal from a bench trial, this court reviews the district court's conclusions of law de novo and findings of fact for clear error. Golden Blount, Inc. v. Robert H. Peterson Co., 365 F.3d 1054, 1058 (Fed.Cir.2004); Brown & Williamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120, 1123 (Fed.Cir.2000). A finding is clearly erroneous when, despite some supporting evidence, "the reviewing court on the entire evidence is left with the definite and firm conviction that a mistake has been committed." United States v. United States Gypsum Co., 333 U.S. 364, 395, 68 S.Ct. 525, 92 L.Ed. 746 (1948).

The court reviews claim construction, a question of law, de novo. Cybor Corp. v. FAS Techs., Inc.,...