Glaxo Wellcome v. Pharmadyne Corp.

• Decision Date: 04 November 1998
• Docket Number: No. Civ. AMD 96-455.,Civ. AMD 96-455.
• Citation: 32 F.Supp.2d 265
• Parties: GLAXO WELLCOME, INC. and Glaxo Group Limited, Plaintiffs, v. PHARMADYNE CORPORATION, et al., Defendants.
• Court: U.S. District Court — District of Maryland

32 F.Supp.2d 265

GLAXO WELLCOME, INC. and Glaxo Group Limited, Plaintiffs, v. PHARMADYNE CORPORATION, et al., Defendants.

No. Civ. AMD 96-455.

United States District Court, D. Maryland.

November 4, 1998.

COPYRIGHT MATERIAL OMITTED

Stephen B. Judlowe, Brian P. Murphy, Robert G. Gibbons, Regina M. Ambery, Jason A. Lief, Hopgood, Calimafde, Kalil & Judlowe, New York City, John Henry Lewin, Jr., Venable, Baetjer & Howard, Baltimore, MD, for Glaxo Wellcome, Inc.

Howard G. Goldberg, Debbie Beschee, Goldberg, Poke & Beschee, Baltimore, MD, John M. Seeberger, Baltimore, MD, Alan H. Bernstein, Robert S. Silver, Caesar, Rivise, Bernstein, Cohen & Pokotilow, Ltd., Philadelphia, PA, James Rubin, West New York City, for Pharmadyne Corp.

FINDINGS OF FACT AND CONCLUSIONS OF LAW

DAVIS, District Judge.

                I.  INTRODUCTION AND PROCEDURAL HISTORY ........................................269
                II. THE PATENTS ................................................................271
                        A. The '431 Patent .....................................................271
                           1.   Background .....................................................271
                

                            2.    Subject Matter Jurisdiction Over the '431 Patent .............272
                                  a. Prior motions for summary judgment as to the '431
                                  Patent .......................................................272
                                  b. The renewed motion for summary judgment as to the
                                  '431 Patent ..................................................273
                       B.  The '790 Patent .....................................................273
                           1. The significance of pH ...........................................273
                           2. The claims of the '790 Patent ....................................274
                           3. Prosecution History ..............................................275
                       C.  The '249 Patent .....................................................277
                           1.    Introduction ..................................................277
                           2.    The addition of ethanol achieves surprising results ...........278
                           3.    The claims of the '249 Patent .................................279
                           4.    Prosecution History ...........................................279
                III.   PHARMADYNE'S DEVELOPMENT OF THE ACCUSED PRODUCT .........................281
                       A.  Introduction ........................................................281
                       B.  The Effort to "Design Around" the Glaxo Patents .....................282
                IV.    ANALYSIS OF LEGAL CLAIMS AND DEFENSES ...................................283
                       A.  Infringement of the '249 Patent .....................................283
                           1.    Doctrine of Equivalents .......................................283
                           2.    Application to the facts in the case at bar ...................284
                       B.  Affirmative Defenses and Declaratory Judgment Issues ................293
                           1.    Obviousness: The '790 and '249 Patents ........................293
                                 a.  Presumption of Validity ...................................293
                                 b.  '790 Prior Art ............................................294
                                       i. Differences ..........................................298
                                 c.  '249 Prior Art ............................................300
                                       i. Differences ..........................................301
                                 d.  Secondary Considerations ..................................303
                                 e.  Ordinary Skill in the Art .................................303
                           2.    Inequitable Conduct ...........................................305
                                 a.  Misconduct in Prosecuting the '431 Patent .................306
                                 b.  Misconduct in Prosecuting the '790 Patent .................307
                                      i. Buffer Concentration ..................................307
                                      ii. The Padfield Article .................................308
                                      iii. The Padfield Declaration ............................309
                                 c.  Misconduct in Prosecuting the '249 Patent .................310
                                      i. Failure to Disclose the Use of Ethanol in Tagamet .....310
                                      ii. The Hempenstall Declaration ..........................311
                V.     CONCLUSION ..............................................................313
                

Glaxo Wellcome, Inc. and Glaxo Group Limited (together "Glaxo"),¹ instituted this action against Pharmadyne Corporation and several affiliated entities for infringement of patents related to its Zantac medication. Defendants counterclaimed for a declaratory judgment on several grounds. A bench trial commenced on November 12, 1997, and concluded on February 5, 1998. The parties have submitted post-trial briefs, which have been carefully considered. I have carefully considered the entire evidentiary record of the case, and render herein findings of fact and conclusions of law in accordance with Fed.R.Civ.P. 52(a).

I. INTRODUCTION AND PROCEDURAL HISTORY

Glaxo develops and manufactures ethical pharmaceutical drugs.² Over the last decade, Glaxo's premiere product has been the anti-ulcer medication Zantac. Zantac became the largest selling drug in the world and has enjoyed unparalleled commercial success in the pharmaceutical industry.³ Glaxo's sales of the various forms of its Zantac product have grossed in excess of $100 million annually for several years. In fact, Glaxo's profits from the sale of Zantac medications have been in the billions of dollars and have helped catapult Glaxo into the position of one of the largest pharmaceutical companies in the world.

The active ingredient in Zantac is the aminoalkyl furan derivative ranitidine hydrochloride. Glaxo scientists were the first to synthesize the chemical compound ranitidine. For several years, Glaxo has fought numerous battles in courtrooms all over the country in a largely successful effort to preserve its property in a series of patents expressed in the Zantac mark. See, e.g., Glaxo Group Ltd. v. TorPharm, Inc., 153 F.3d 1366, 1367 (Fed.Cir.1998) ("This is yet another appeal in the ongoing litigation between the holder of patents on a popular medication, Zantac, and a number of generic drug companies who are attempting to sell a generic equivalent of the drug...."); Glaxo, Inc. v. Novopharm Ltd., 110 F.3d 1562 (Fed.Cir.1997); Glaxo Inc. v. Novopharm Ltd., 52 F.3d 1043 (Fed.Cir. 1995).

In 1977, Glaxo's Dr. David Collin synthesized the crystalline-salt form of the ranitidine now used in Glaxo's Zantac drug products. Ranitidine's unique qualities make it a highly marketable drug. Ranitidine is more potent than other anti-ulcer medications on the market.⁴ In addition, ranitidine does not cause some of the side effects produced by other anti-ulcer drugs, such as impotence, breast formation in males, and certain endocrine problems.

Glaxo Group Limited holds the three United States patents which are the subject of this litigation — U.S. Patent Nos. 4,521,431 ("the '431 patent"), 4,585,790 ("the '790 patent"), and 5,068,249 ("the '249 patent"). All three patents include ranitidine in a pharmaceutical formulation. In the formulations at issue in this case, Glaxo's ranitidine hydrochloride is dispensed as an oral syrup and injectable product. The syrup formulation is particularly important for children, the elderly and infirm, and adults who are not able to take medication in pill form. Injectable, i.e., intravenous, formulations of Zantac (hereafter "Zantac injection"), covered by the '790 patent, are used particularly for patients who are otherwise receiving intravenous fluids, or those who are unconscious or comatose.

Defendants UDL Laboratories, Inc., Florida, AndaPharma Corporation, and Pharmadyne Corporation are subsidiaries of UDL Laboratories, Inc., Illinois. Defendant UDL Laboratories, Inc. is an Illinois corporation. UDL Laboratories, Inc., Illinois repackages and markets generic pharmaceuticals. Its counterpart in Florida manufactures and packages liquid generic pharmaceuticals. Pharmadyne and AndaPharma were created by UDL for the sole purpose of developing a ranitidine hydrochloride oral solution.⁵

Pharmadyne contracted with UDL to have UDL research, develop, manufacture, test and ultimately distribute Pharmadyne's ranitidine hydrochloride oral syrup in the United States. Pharmadyne also contracted with UDL to act as its agent to prepare an Abbreviated New Drug application ("ANDA") concerning ranitidine hydrochloride oral syrup solely for filing by Pharmadyne with the Food and Drug Administration ("FDA").⁶ In November 1995, Pharmadyne submitted its ANDA No. 74-794 seeking approval from the FDA to market ranitidine oral solution USP in the United States, pursuant to 21 U.S.C.A. § 355(j). Pharmadyne's ANDA contained a paragraph IV certification and thus Pharmadyne committed a "highly artificial act of patent infringement" under 35 U.S.C.A. § 271(e)(2).

Under 35 U.S.C.A. § 271(e)(2)(A):

It shall be an act of infringement to submit (A) an application under section 5050 of the Federal Food, Drug, and Cosmetic Act or as described in section 505(b)(2) of such Act for a drug claimed in a patent or the use of which is claimed in a patent, ... if the purpose of such submission is to obtain approval under such Act to engage in the commercial manufacture, use, or sale of a drug ... claimed in a patent or the use of which is claimed in a patent before the expiration of such patent.

See generally Eli Lilly and Co. v. Medtronic, Inc., 496 U.S. 661, 676, 110 S.Ct. 2683, 110 L.Ed.2d 605, reh'g denied, 497 U.S. 1047, 111 S.Ct. 11, 111 L.Ed.2d 825 (1990); Glaxo v. Novopharm, Ltd., 110 F.3d 1562, 1568-69 (Fed.Cir.1997), aff'g, 931 F.Supp. 1280 (E.D.N.C.1996).

On December 27, 1995, Pharmadyne notified Glaxo that Pharmadyne was seeking approval from the FDA to market...