Pfizer Inc. v. Teva Pharmaceuticals Usa, Inc., No. CIV.A. 04-754(JCL).

• Court: United States District Courts. 3th Circuit. United States District Courts. 3th Circuit. District of New Jersey
• Writing for the Court: Lifland
• Citation: 482 F.Supp.2d 390
• Parties: PFIZER INC., Pharmacia Corp., Pharmacia & Upjohn Inc., Pharmacia & Upjohn Company, G.D. Searle & Co., G.D. Searle LLC, Searle LLC (Delaware) and Searle LLC (Nevada) Plaintiffs, v. TEVA PHARMACEUTICALS USA, INC. Defendant.
• Decision Date: 20 March 2007
• Docket Number: No. CIV.A. 04-754(JCL).

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482 F.Supp.2d 390 PFIZER INC., Pharmacia Corp., Pharmacia & Upjohn Inc., Pharmacia & Upjohn Company, G.D. Searle & Co., G.D. Searle LLC, Searle LLC (Delaware) and Searle LLC (Nevada) Plaintiffs,
v.
TEVA PHARMACEUTICALS USA, INC. Defendant. No. CIV.A. 04-754(JCL). United States District Court, D. New Jersey. March 20, 2007.

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David E. Delorenzi, Sheila F. McShane, Gibbons, Del Deo, Dolan, Griffinger & Vecchione, PC, Newark, NJ, for Plaintiffs.

Michael E. Patunas, Lite Depalma Greenberg & Rivas, LLC, Newark, NJ, for Defendant.

FINDINGS OF FACT AND CONCLUSIONS OF LAW

LIFLAND, District Judge.

Plaintiffs, Pfizer, Inc., Pharmacia Corp., Pharmacia & Upjohn Inc., Pharmacia & Upjohn Company, G.D. Searle & Co., G.D. Searle LLC, Searle LLC (Delaware), and Searle LLC (Nevada) (collectively "Pfizer" or "Plaintiffs") allege infringement of U.S. Patent Nos. 5,466,823 (the "'823 Patent"); 5,563,165 (the "'165 Patent"); and 5,760,068 (the "'068 Patent") (collectively the "patents-in-suit") by Teva Pharmaceuticals U.S.A., Inc. ("Teva" or "Defendant"). The patents-in-suit are directed toward celecoxib, the active ingredient in Celebrex, and a broad genus of compounds that includes

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celecoxib, pharmaceutical compositions including such compounds, and methods of using such compounds.

For the reasons set forth below,¹ the Court finds that Teva has failed to prove obviousness, inequitable conduct, a violation of the best mode requirement, or obvious-type double patenting by clear and convincing evidence. Thus, the patents are neither invalid nor unenforceable, and Teva has infringed the patents under 35 U.S.C. § 271(e)(2).

BACKGROUND

I. A Brief History of Anti-Inflammatory Drugs

The precise biological reason people suffer from pain and inflammation is not yet fully understood. However, great progress has been made in recent decades toward understanding and treating the pain and other symptoms associated with inflammatory conditions. Around the turn of the century, researchers at Friedrich Bayer & Co. invented aspirin, which quickly gained popularity as a painkiller. Over the next several decades similar drugs — classified as traditional non-steroidal anti-inflammatory drugs ("NSAIDs") — were introduced into the market, including ibuprofen and naproxen. Yet it was not until the early 1970s that the mechanism of action of these drugs was understood. In simplified terms, scientists eventually discerned that traditional NSAIDs worked by blocking the production of prostaglandins in cells. Prostaglandins are small molecules that are associated with both pain and inflammation, and with "good housekeeping" functions, such as contributing to good gastrointestinal physiology and blood clotting. These prostaglandin molecules are produced in the body when arachidonic acid (a fat found in cell membranes) is catalyzed by cyclooxygenase (COX) enzymes. Traditional NSAIDs inhibited the COX enzyme, thus preventing the creation of prostaglandins and the associated pain and inflammation.

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This discovery also shed light on the cause of some of the reported side effects of traditional NSAIDs. It had been known for some time that NSAIDs were associated with gastrointestinal ("GI") side effects, ranging from discomfort to serious life threatening ulcers, yet the cause of these GI risks was unclear. With the discovery

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of the prostaglandin pathway, it became clear that in addition to reducing the negative effects of prostaglandins, traditional NSAIDs like aspirin also reduced the positive "housekeeping" functions, thus causing potentially severe GI risks. This new knowledge was an important step in the ongoing effort to invent a new kind of NSAID that would treat pain and inflammation without causing GI side effects.

The next breakthrough in anti-inflammatory drug development came in the 1970s and 1980s when scientists, established that there were in fact two different kinds of COX enzymes: one responsible for producing good housekeeping prostaglandins (COX-1), and, one responsible for producing prostaglandins associated with pain and inflammation (COX-2). (See figure below.)

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COX-1 was fully identified and sequenced in 1988. COX-2 was sequenced in 1991. Once both enzymes were sequenced, scientists hypothesized that it might be possible to selectively inhibit COX-2, thus creating a GI sparing NSAID. However, due to the similarity of the two enzymes, there was significant skepticism as to whether it would be possible to develop a drug that selectively inhibited either enzyme.

Scientists became more hopeful in 1992 after Dr. William Galbraith of DuPont-Merck gave a presentation at a prostaglandin conference in Keystone, Colorado ("the Keystone Conference"). Dr. Galbraith's presentation focused on a compound called DuP 697, which he reported might be a COX-2 selective inhibitor. Following the Keystone Conference, pharmaceutical companies stepped up their efforts to create a COX-2 selective compound, and thus began what Teva has characterized as a "race" to develop the first COX-2 selective inhibitor, with Pfizer and Merck as the two frontrunners.

II. Celebrex and the Patents-in-Suit

For Pfizer, the finish line of the COX-2 selective inhibitor race was Celebrex. Sometime between August and November 1993,² Pfizer scientists invented several

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new compounds they believed would selectively inhibit the COX-2 enzyme. One of the compounds was celecoxib.

On November 30, 1993, Pfizer filed U.S. Application No. 08/160,594 (the "'594 Application"), covering a broad range of chemical compounds, as well as pharmaceutical compositions utilizing the compounds, and methods of treatment. On July 12, 1994, the Patent Examiner issued a restriction requirement requiring Pfizer to select either the compound claims, the composition claims, or the method claims to prosecute, and further required Pfizer to elect a single species within the chosen group for examination.

Pfizer elected to prosecute the compound claims and chose the species described in example # 1c (celecoxib) as the elected species. The Examiner then defined a "generic concept inclusive of the elected species ... for examination along with the elected species." The '594 Application, as narrowed, was approved and ultimately issued as the '823 Patent. Pfizer filed several divisional applications covering the compounds that were not embraced by the '823 Patent. These patents were issued, but are not relevant here. Pfizer also filed a divisional application covering compositions. This divisional application issued as the '165 Patent. Finally, Pfizer also filed international application PCT12720 covering methods. This application entered the national stage as the '113 Application, and ultimately issued as the '068 Patent. (See figure below.)

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After the patents-in-suit were issued, Pfizer scientists conducted further testing of the compounds covered by the patents to identify a compound to develop into a commercial drug. Several compounds that initially seemed to be promising candidates were discarded after further testing revealed unacceptable properties such as excessive half-life or liver toxicity. Eventually, scientists selected celecoxib as the preferred compound and, following clinical trials, submitted a New Drug Application to the Food and Drug Administration ("FDA") for Celebrex. The FDA approved

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Celebrex as a COX-2 selective NSAID for the treatment of osteoarthritis and rheumatoid arthritis on December 31, 1998. Celebrex was launched the following year, and almost immediately achieved enormous and sustained success in the marketplace.

III. Teva's Abbreviated New Drug Application

The Hatch-Waxman Amendments to the Federal Food, Drug, and Cosmetic Act permit an applicant to file an Abbreviated New Drug Application ("ANDA") with the Food and Drug Administration ("FDA") requesting approval of a bioequivalent ("generic") version of a drug that is already listed by the FDA as approved for safety and effectiveness without having to submit additional safety and efficacy data. See 21 U.S.C. § 355(j)(2)(A). An ANDA may be filed for drugs currently protected by patents. In its filing, the applicant must certify either (1) that it will not market its drug prior to the expiration of the relevant patents, or (2) that the relevant patents "are invalid or will not be infringed by the manufacture, use or sale of the new drug for which the ANDA is submitted." 21 U.S.C. § 355(j)(2)(A)(vii)(IV). An ANDA applicant filing its application with the FDA and making a Section IV certification must notify the holder of the patent, who may then bring an action against the applicant for infringement under 35 U.S.C. § 271(e)(2). See 21 U.S.C. §§ 355(j)(2)(B)(i) and (j)(5)(B)(iii); see also, e.g., SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1314 (Fed. Cir.2006). Submission of an ANDA is an act of patent infringement if the ANDA seeks approval to manufacture, use, or sell a drug that is claimed in a patent or the use of which is claimed in a patent. 35 U.S.C. § 271(e).

Teva filed Abbreviated New Drug Application No. 76-898 with the FDA. The application was addressed to a proposed drug March 19, 2007 product identified as "Celecoxib Capsules, 100 mg, 200 mg, and 400 mg." The ANDA contained a Section IV certification challenging the validity of the patents covering celecoxib.

IV. The Current Litigation

In February 2004, Pfizer filed an action against Teva for infringement. In May 2004, Teva filed an answer and asserted an affirmative defense claiming that the patents-in-suit are invalid or unenforceable due to obviousness under 35 U.S.C. § 103(a),...