Sanofi-Synthelabo v. Apotex Inc.

488 F.Supp.2d 317

SANOFI-SYNTHELABO; Sanofi-Synthelabo, Inc.; and Bristol-Myers Squibb Sanofi Pharmaceuticals Holding Partnership, Plaintiffs, v. APOTEX INC.; and Apotex Corp., Defendants.

No. 02 Civ. 2255(SHS).

United States District Court, S.D. New York.

August 31, 2006.

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Evan R. Chesler, Richard J. Stark and David Greenwald, Cravath Swaine Moore LLP, New York, NY, for Plaintiffs.

Allan H. Fried, Caesar, Rivise, Bernstein, Cohen & Pokotilow, Ltd., New York, NY, Bruce J. Chasan, Kevin A. Keeling, Mona Gupta, Caesar, Rivise, Bernstein, Cohen & Pokotilow, Ltd., Philadelphia, PA, Karen J. Bernstein, Pryor Cashman Sherman & Fynn LLP, New York, NY, for Defendants.

OPINION

STEIN, District Judge.

                               TABLE OF CONTENTS
  I.  OVERVIEW ...............................................................321
 II.  BACKGROUND .............................................................322
      A.  History of this Action .............................................322
      B.  Events Giving Rise to This Motion ..................................323
III.  PRELIMINARY INJUNCTION .................................................325
      A.  Legal Standard .....................................................325
      B.  Likelihood of Success ..............................................326
          1.  Infringement ...................................................326
          2.  Invalidity .....................................................327
              a.  Anticipation ...............................................327
                    i.  Legal Standards ......................................327
                   ii.  The '596 and '265 Patents ............................328
                  iii.  Apotex's Case for Anticipation .......................329
                   iv.  Discussion ...........................................330
                    v.  Conclusion ...........................................335
              b.  Obviousness ................................................335
              c.  Double-Patenting ...........................................338
          3.  Unenforceability ...............................................338

              a.  General Principles .........................................338
              b.  Analysis ...................................................339
                    i.  "Unexpected" Therapeutic Activity ....................339
                   ii.  Tolerance ............................................340
                  iii.  Dr. Maffrand's Knowledge .............................341
              c.  Conclusion .................................................341
      C.  Irreparable Harm ...................................................342
      D.  Balance of Hardships ...............................................344
      E.  Public Interest ....................................................345
 IV.  DEFENSES ...............................................................346
      A.  Laches .............................................................346
      B.  Unclean Hands ......................................................348
  V.  REMEDY .................................................................348
      A.  Injunction .........................................................348
      B.  Bond ...............................................................349
 VI.  CONCLUSION .............................................................350

I. OVERVIEW

Plavix, the most widely prescribed prescription blood-thinning agent in the world, prevents platelets in blood from aggregating around obstructions — such as metal stents or cholesterol deposits — in arterial passageways. Forty-eight million Americans take Plavix daily to prevent potentially fatal blood clots. This action arose between Sanofi-Aventis, Sanofi-Synthelabo, Inc. and Bristol-Myers Squibb Sanofi Pharmaceuticals Holding Partnership (collectively, "Sanofi") — those entities that invested in the research and development to patent this drug and bring it to market — on the one hand, and Apotex, Inc. and Apotex Corporation (collectively, "Apotex") — which seeks to market the generic equivalent of Plavix — on the other. Before the Court is a motion by Sanofi to preliminarily enjoin Apotex from distributing its generic version of Plavix in the United States after an at-risk launch of that drug by Apotex approximately three weeks ago, on August 8, 2006. Sanofi seeks to enjoin Apotex from any further distribution of the generic drug pending an ultimate decision on the merits of this action and has also requested that the Court order a recall of the product already distributed.

In this action, the parties have agreed and stipulated that Apotex's generic product in fact infringes Sanofi's patent. Apotex does not dispute that but rather claims that Sanofi's patent is invalid and unenforceable. Because Sanofi has adequately demonstrated that the questions Apotex raises as to the validity and enforceability of Sanofi's '265 patent are without substantial merit based on the evidence adduced to date, Sanofi has demonstrated a likelihood of success on the merits at trial. Further, Sanofi will suffer irreparable harm due to Apotex's continued distribution of the infringing pharmaceutical, and Apotex's hardships primarily arise from the company's own calculated risk-taking. Finally, although there are competing — and substantial — public interests at stake on both sides of this litigation, the balance of those competing public interests slightly favors Sanofi. For these reasons, and because the Court finds Apotex's laches and unclean hands defenses to be without merit, Sanofi's motion is granted insofar as Apotex is enjoined from further distribution of its generic product. Sanofi's motion is denied insofar as it requests a recall of the product Apotex has already distributed.

II. BACKGROUND

In the context of the Court's consideration of a motion for a preliminary injunction, "all findings of fact and conclusions of law ... are subject to change upon the ultimate trial on the merits." Purdue Pharma L.P. v. Boehringer Ingelheim GmbH, 237 F.3d 1359, 1363 (Fed.Cir.2001) (citing Illinois Tool Works, Inc. v. Grip-Pak, Inc., 906 F.2d 679, 681 (Fed.Cir. 1990)); University of Texas v. Camenisch, 451 U.S. 390, 395, 101 S.Ct. 1830, 1834, 68 L.Ed.2d 175 (1981). The Court finds the following facts for the purposes of this Opinion.

A. History of this Action

Plavix, approved for sale in the United States by the U.S. Food and Drug Administration ("FDA") in November 1997, is prescribed for the reduction of thrombotic events, such as heart attacks and strokes, for patients who have recently suffered such events or who have arterial disease or acute coronary syndrome. (See Stipulated Statement of Facts ("Fact Stmt"), attached as Ex. A to Joint Pretrial Order dated May 27, 2005 at ¶ 12.) The active ingredient of Plavix is clopidogrel bisulfate. (Id.) Sanofi obtained a patent claiming clopidogrel bisulfate on July 11, 1989, naming Sanofi employees Alain Badorc and Daniel Fréhel as inventors. (Id. at ¶¶ 8-9.) That patent, U.S. patent number 4,847,265 ("the '265 patent"), claims clopidogrel bisulfate by its chemical name in claim three: "hydrogen sulfate of the dextrorotatory isomer of methyl alpha 5(4,5,6,7-tetrahydro(3,2-c)thieno pyridyl)(2-chlorophenyl)-acetate substantially separated from the levo-rotatory isomer." (Id. at ¶¶ 9-10.) The '265 patent is exclusively licensed to the Bristol-Myers Squibb Sanofi Pharmaceuticals Holding Partnership and expires on November 17, 2011. (Id. at ¶ 9.)

Apotex sought approval from the FDA to manufacture and sell clopidogrel bisulfate tablets before the expiration of Sanofi's '265 patent by filing an Abbreviated New Drug Application ("ANDA") with the FDA in November 2001. (Fact Stmt at ¶¶ 14-15.) In the ANDA, Apotex certified that it believed the '265 patent to be invalid, pursuant to the requirements of 21 U.S.C. § 355(j)(2)(vii)(IV). (Id. at ¶ 16; see Glaxo Group Ltd. v. Apotex, Inc., 376 F.3d 1339, 1344 (Fed.Cir.2004) (pursuant to 21 U.S.C. § 355(j)(2)(A)(I)-(IV), a generic company has an obligation to "certify that either (I) no patent information is listed ... for the proposed generic drug; (II) that the listed patents have expired; (III) that the listed patents will expire before the generic company markets its product; or (IV) that the patents listed are invalid or will not be infringed by the generic drug.").) Apotex was the first to file an ANDA for clopidogrel bisulfate (Decl. of Dr. Bernard Sherman, dated Aug. 16, 2006 ("Sherman Decl.") at ¶ 17), thereby securing the right to 180 days of market exclusivity provided by the Hatch-Waxman Act to the first ANDA filer to challenge a patent. See 21 U.S.C. § 355(j)(5)(B)(iv); see also In re Tamoxifen Citrate Antitrust Litig., 429 F.3d 370, 376 (2d Cir.2005).

In response to that ANDA filing by Apotex, Sanofi filed this suit against Apotex on March 21, 2002 pursuant to 35 U.S.C. § 271(e), on the ground that Apotex's filing of the ANDA constituted infringement of the '265 patent. Section 271(e)(2)(A) provides that "it shall be an act of infringement to submit (A) an application ... for a drug claimed in a patent or the use of which is claimed in such a patent, ... if the purpose of such submission is to obtain approval ... to engage in the commercial manufacture, use, or sale" of the drug before the expiration of the patent. See also Glaxo Group, 376 F.3d at 1344 ("Section 271(e)(2)(A) provides a jurisdictional basis for a declaratory judgment suit against a generic manufacturer."); Glaxo, Inc. v. Novopharm Ltd., 110 F.3d 1562, 1569 (Fed.Cir.1997) ("§ 271(e)(2) provided patentees with a defined act of infringement sufficient to create case or controversy jurisdiction to enable a court to promptly...