Alcon, Inc. v. Teva Pharmaceuticals Usa, Inc.

• Decision Date: 19 October 2009
• Docket Number: Civ. No. 06-234-SLR.
• Citation: 664 F.Supp.2d 443
• Parties: ALCON, INC. and Alcon Research, Ltd., Plaintiffs, v. TEVA PHARMACEUTICALS USA, INC., Defendant.
• Court: U.S. District Court — District of Delaware

664 F.Supp.2d 443

ALCON, INC. and Alcon Research, Ltd., Plaintiffs, v. TEVA PHARMACEUTICALS USA, INC., Defendant.

Civ. No. 06-234-SLR.

United States District Court, D. Delaware.

October 19, 2009.

COPYRIGHT MATERIAL OMITTED

COPYRIGHT MATERIAL OMITTED

Frederick L. Cottrell, III, Esquire, Jeffrey L. Moyer, Esquire, and Anne Shea Gaza, Esquire, of Richards, Layton & Finger P.A., Wilmington, DE, Of Counsel

Bruce R. Genderson, Esquire, Adam L. Perlman, Esquire, David I. Berl, Esquire, Dov P. Grossman, Esquire, and Stanley E. Fisher, Esquire, of Williams & Connolly LLP, Washington, D.C., for Plaintiffs.

Richard D. Kirk, Esquire, and Ashley B. Stitzer, Esquire, of Bayard, P.A., Wilmington, DE, Of Counsel Bruce M. Gagala, Esquire, M. Daniel Hefner, Esquire, and Douglas A. Robinson, Esquire, of Leydig, Voit & Mayer, Ltd., Chicago, IL, for Defendant.

OPINION

SUE L. ROBINSON, District Judge.

I. INTRODUCTION

This action arises out of the filing of an Abbreviated New Drug Application ("ANDA")¹ by defendant Teva Pharmaceuticals USA, Inc. ("Teva") to market a generic version of the antibacterial drug VIGAMOX® proprietary to plaintiffs Alcon, Inc., and Alcon Manufacturing, Ltd. (now part of Alcon Research, Ltd.)² (collectively, "Alcon"). VIGAMOX® is a topical ophthalmic solution comprised of the active ingredient moxifloxacin hydrochloride, which is protected by, inter alia, U.S. Patent No. 6,716,830 ("the '830 patent"). Teva's ANDA asserts a "Paragraph IV Certification," and seeks approval to market a generic equivalent of VIGAMOX® prior to the expiration of the '830 patent. See 21 U.S.C. § 355(j)(2)(A)(vii)(IV). Alcon brought this suit against Teva on April 5, 2006, alleging infringement of the '830 patent pursuant to 35 U.S.C. § 271(e)(2)(A).³ (D.I. 1)

A bench trial commenced February 28, 2008, principally to determine: (1) whether Teva's proposed generic equivalent ("the ANDA product") contains moxifloxacin and so infringes claim 1 of the '830 patent; and (2) whether claim 1 is invalid for anticipation, obviousness or failure to satisfy the best mode, written description, and enablement requirements of 35 U.S.C. § 112. (Id. at 4-5) The issues were fully briefed post-trial. (D.I. 93; D.I. 107; D.I. 108; D.I. 111; D.I. 112; D.I. 115)

The court has jurisdiction over this action pursuant to 28 U.S.C. §§ 1331, 1338(a), 2201, and 2202. Having considered the documentary evidence and testimony, the court makes the following findings of fact and conclusions of law pursuant to Fed.R.Civ.P. 52(a).

II. FINDINGS OF FACT

A. Parties

Plaintiff Alcon, Inc. is a Swiss corporation with its principal place of business in Hunenberg, Switzerland. (D.I. 79, ex. 1 at ¶ 3) It is the assignee and owner of the '830 patent. (Id. at ¶ 23) Plaintiff Alcon Research, Ltd., is a Delaware corporation with its principal place of business in Fort Worth, Texas. (Id. at ¶ 4) It is the exclusive licensee of the '830 patent. (Id. at ¶ 24)

Alcon sells a topical ophthalmic pharmaceutical solution under the tradename VIGAMOX®. (Id. at ¶ 26) Alcon is the holder of a Food and Drug Administration ("FDA")-approved New Drug Application ("NDA") for VIGAMOX® and has listed the '830 patent, among others, in the FDA's Orange Book for VIGAMOX®. (Id. at ¶ 28)

Teva is a wholly-owned subsidiary of Teva Pharmaceuticals Industries, Ltd. (Id. at ¶ 59) Teva is a Delaware corporation with its principal place of business in Pennsylvania. (Id. at ¶ 5) Teva engages primarily in the manufacturing and marketing of generic drugs.

B. Moxifloxacin

Quinolone carboxylic acids, or "quinolones," are a class of antibacterial compounds that share a common core chemical structure, depicted as follows:

NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE

(See PTX 2003) The numbers along the diagram of the molecule represent positions at which functional groups may attach. (D.I. 100 at 54-55) The "COOH" at the 3-position represents a carboxylic acid. (Id. at 55) A carboxylic acid at the 3-position, along with a nitrogen-containing carbon ring and a double-bonded oxygen, are fundamental and common aspects of all quinolone antibiotics. (Id.)

Prior to July 28, 1998, the World Health Organization ("WHO") proposed the international nonproprietary name ("INN") "moxifloxacin"⁴ for the quinolone depicted below:

NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE

(D.I. 100 at 60; PTX 139 at 187) Moxifloxacin, like other quinolones, possesses a carboxylic acid at the 3-position, double-bonded oxygen and a nitrogen-containing fused carbon ring. (PTX 3 at col. 98, II. 55-65) The bicyclic amine attached at the 7-position, a feature that distinguishes moxifloxacin from other quinolones, contains two chiral carbons. Because of these two chiral carbons, there are four possible stereochemical arrangements⁵ for this molecule. (D.I. 79, ex. 1 at ¶ 68) Two of these arrangements are cis isomers, and the remaining two are trans isomers.⁶ (Id.) The two cis compounds (denoted as "S,S" and "R,R") act as mirror images of each other, thus constituting a pair of enantiomers, while the two trans compounds ("S,R" and "R,S") constitute a second pair of enantiomers. (Id.) Often, enantiomers will significantly differ from each other in terms of pharmocology.⁷

Moxifloxacin has an "S,S" configuration at the chiral carbons in the 7-position bicyclic amine. (Id. at ¶ 70) The bolded carbon-hydrogen bonds in the figure above depict this configuration, indicating that the bonds extend upward from the rest of the molecule, which exists in the plane of the page. By contrast, the carbon-hydrogen bonds at the chiral carbons of the corresponding compound with the "R,R" configuration (the "R,R enantiomer") would extend downward beyond the plane of the paper. (Id.) These graphical conventions are unnecessary for named structures with known stereochemistry; the name imparts such information. (D.I. 100 at 85)

Bayer AG ("Bayer") began developing moxifloxacin under the guise of BAY 12-8039, the company's designation of moxifloxacin hydrochloride ("moxifloxacin HCI"). (Id. at 135) Bayer is the holder of U.S. Patent No. 5,607,942 (the '942 patent),⁸ which claims the compound moxifloxacin⁹ and its sterioisomers. (PTX 3 at col. 98, I. 51-col. 99, 1. 2) BAY 12-8039 became the subject of several studies with respect to its efficacy in combating gram-positive and gram-negative bacteria. (PTX 1124; PTX 1125; PTX 137) The specification of the '942 patent itself generally describes the efficacy of the numerous compounds disclosed as "exhibit[ing] a broad antibacterial spectrum against Gram-negative and Gram-positive bacteria...." (PTX 3 at col. 53, II. 22-27)

Satisfied with the pharmaceutical potential of BAY 12-8039, Bayer filed a NDA under the tradename AVELOX® with the FDA. This application was directed towards a 400 mg tablet form of moxifloxacin. (D.I. 105 at 1052) As of 1996, BAY 12-8039 had entered into Phase II of the NDA process. (PTX 1098) However, only Phase I¹⁰ toxicity data for moxifloxacin was available as of September 1998. (D.I. 103 at 906-07) The FDA approved Bayer's NDA for AVELOX® on December 10, 1999. (D.I. 104 at 1051)

C. The Invention and the '830 Patent

Dr. David Stroman is a clinical microbiologist employed by Alcon who is also involved in the selection and screening of potential ophthalmic and otic compositions. (D.I. 102 at 565, 570-571) At trial, Dr. Stroman testified that, in 1998, the focus in the art was upon the need to develop efficacious treatments for intraocular infections caused by Staphylococcus aureus, a gram-positive bacteria, and Pseudomonas aeruginosa, a gram-negative bacteria. (Id. at 566) Alcon, specifically, sought a compound that could both treat infections caused by these pathogens and act as a prophylactic measure to prevent infection at the time of surgery. (Id. at 569)

Both pathogens, which cause sight-threatening infections inside the eye, displayed emerging resistance¹¹ to quinolone treatment. (Id.) However, resistance to Pseudomonas aeruginosa caused investigators greater concern, because it was considered the most threatening ocular pathogen. (Id.) Maintaining activity against Pseudomonas aeruginosa while enhancing activity against Staphylococcus aureus became objectives of the search. (D.I. 101 at 402) In 1998, ciprofloxacin,¹² the then-state-of-the-art treatment for ophthalmic infections, served as the standard for microbiological activity against ocular pathogens. (D.I. 102 at 568; D.I. 103 at 856)

Dr. Stroman further testified that, by contrast, the medical community had no need for new treatments solely for surface infections, such as conjunctivitis.¹³ (D.I. 101 at 389-91; D.I. 102 at 566-67; D.I. 103 at 844-45) Such infections held little chance of causing serious damage, were adequately controlled by existing products and often resolved without treatment. (Id.)

These parameters guided Dr. Stroman's analysis of roughly one hundred compounds between 1990 (when he joined Alcon) and 1998. (D.I. 102 at 570) He encountered in vitro data for BAY 12-8039 on a Bayer poster at the 1997 ICAAC¹⁴ conference in Toronto. (Id. at 571; PTX 1098) This data indicated that, while BAY 12-8039 was more active than ciprofloxacin against Staphylococcus aureus, it was eight times less active against Pseudomonas aeruginosa. (Id.) Dr. Stroman left the conference with a list of 10-15 compounds that he had interest in obtaining for further analysis. (Id. at 572) Despite his concerns about the in vitro activity data, Dr. Stroman requested from Bayer a sample of BAY 12-8039. (D.I. 103 at 645; PTX 1065)

Dr. Stroman received a 10 gram sample of BAY 12-8039 on January 4, 1999. (Id. at 585; PTX 89) A multi-departmental investigation confirmed Bayer's in vitro data for BAY 12-8039. (D.I. 102 at 591) However, an in vivo test¹⁵ of the sample painted a different picture. (D.I. 102 at 594-95) When applied as a topical ophthalmic composition, moxifloxacin was shown to treat and...