Pfizer Inc. v. Teva Pharmas. USA, Inc.

• Decision Date: 12 August 2011
• Docket Number: Civil No. 2:10cv128.
• Citation: 80 Fed.R.Serv.3d 966,803 F.Supp.2d 409
• Court: U.S. District Court — Eastern District of Virginia
• Parties: PFIZER INC., Pfizer Ltd., and Pfizer Ireland Pharmaceuticals Unlimited Liability Co., Plaintiffs and Counterclaim Defendants, v. TEVA PHARMACEUTICALS USA, INC., Defendant and Counterclaim Plaintiff.

80 Fed.R.Serv.3d 966

803 F.Supp.2d 409

PFIZER INC., Pfizer Ltd., and Pfizer Ireland Pharmaceuticals Unlimited Liability Co., Plaintiffs and Counterclaim Defendants,

v.TEVA PHARMACEUTICALS USA, INC., Defendant and Counterclaim Plaintiff.

Civil No. 2:10cv128.

United States District Court, E.D. Virginia,Norfolk Division.

Aug. 12, 2011.

Conrad M. Sumadine, Esq., Willcox & Savage PC, Norfolk, VA, Daniel P. DiNapoli, Esq., Aaron Stiefel, Esq., Soumitra Deka, Esq., Steven J. Glassman, Kaye Scholer LLP, New York, NY, for Plaintiffs.

Gregory N. Stillman, Esq., Hunton & Williams, Norfolk, VA, Kevin J. Culligan, Esq., Keith A. Zullow, Esq., John P. Hanish, Esq., Goodwin Procter LLP, New York, NY, for Defendant.

OPINION AND FINAL ORDER

REBECCA BEACH SMITH, District Judge.

On March 24, 2010, Pfizer, Inc., Pfizer, Ltd., and Pfizer Ireland Pharmaceuticals Partnership ¹ (collectively “Pfizer”) ² filed suit in this court against Teva Pharmaceuticals USA, Inc. (“Teva”) ³ alleging imminent infringement of Pfizer's United States Patent No. 6,469,012 (“the '012 patent”), entitled “Pyrazolopyrimidinones for the Treatment of Impotence.” United States Patent No. 6,469,012 (filed May 13, 1994) (issued Oct. 22, 2002), Plaintiff's Exhibit (hereinafter referred to as “PTX”) 0001. The ' 012 patent claims the use of certain chemical compounds as a method of treating erectile dysfunction (“ED”). Only Claims 25 and 26 of the ' 012 patent are in dispute in this case. See Pfizer, Inc. v. Teva Pharms. USA, Inc., No. 2:10cv128, 803 F.Supp.2d 459, 463–64, 2011 WL 3610654 (E.D.Va. Jan. 18, 2011) (noting that only these claims are at issue in this case), Docket # 77.⁴

One of the especially preferred compounds of the '012 patent is sildenafil, the active ingredient in the ED drug Viagra.⁵ On October 25, 2004, Teva filed an Abbreviated New Drug Application with the Food and Drug Administration (“FDA”) seeking approval to market a generic equivalent of Viagra containing sildenafil citrate. See PTX 238. On April 24, 2007, the FDA granted Teva tentative approval to do so.⁶ Pfizer alleges in its Amended Complaint that Teva's planned generic drug will infringe the ' 012 patent, and seeks a declaration from the court to that effect.

On April 29, 2010, Teva answered the Complaint and filed a Counterclaim against Pfizer seeking a declaration that Teva's planned drug will not infringe the '012 patent and that the claims of the '012 patent are invalid. Teva subsequently sought, and was granted, leave of the court to file an Amended Answer and Counterclaim, which amendment added an allegation that the '012 patent is invalid because of inequitable conduct committed during its prosecution before the Patent and Trademark Office (“PTO”).⁷ On December 13, 2010, this court held a hearing pursuant to Markman v. Westview Instruments, Inc., 517 U.S. 370, 372, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996), and issued an opinion on March 17, 2011, construing the disputed terms of the patent. See Pfizer, Inc. v. Teva Pharms. USA, Inc., 803 F.Supp.2d 397, 2011 WL 996794 (E.D.Va.2011).

A bench trial in this case commenced on June 15, 2011, lasting for twelve days. At trial, Teva stipulated to infringement, and therefore this issue is not before the court. See Docket # 330. On July 17, 2011, after final arguments had concluded, this court took all outstanding issues under advisement. This Opinion and Final Order addresses and resolves all remaining motions and merits determinations.

I. Factual Overview

The patent in suit in this case is the '012 patent, and in particular Claims 25 and 26, which claim:

25. A method of treating erectile dysfunction in a male human, comprising orally administering to a male human in need of such treatment an effective amount of a compound selected from:

[listing nine different chemical compounds]

or a pharmaceutically acceptable salt thereof;

or a pharmaceutical composition containing either entity.

26. A method as defined in claim 25, wherein said compound is [listing a chemical compound] or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity.

'012 patent col. 10, lines 1–39, PTX 0001.⁸ Thus, these claims of the patent teach the oral administration of sildenafil and other compounds for the treatment of ED.⁹ The ' 012 patent will expire on October 22, 2019. See Final Pretrial Order ¶ 9, Docket # 267.¹⁰

As the patent in suit concerns the treatment of ED, bringing with it a host of technical terminology and a background of underlying knowledge, this court will first review the biology and physiology of erections ¹¹ and then will move to a description of the invention and patents concerned.

A.¹²

The penis of a male human contains erectile tissue called the corpus cavernosum, consisting of two corpora cavernosa that run its length. The corpus cavernosum is smooth muscle tissue that is spongy and composed of cavernosal spaces which can expand and fill with blood to produce an erection. The corpus cavernosum is surrounded by fibrous tissue known as the tunica albuginea. When the penis is in a flaccid state, the corpus cavernosum is contracted. An erection is produced when the corpus cavernosum relaxes so that it expands and fills with blood. As the corpus cavernosum relaxes, the tunica albuginea compresses the veins that drain blood from the penis, thus preventing blood from flowing out and raising pressure inside the penis, producing an erection. Detumescence of the penis occurs when the corpus cavernosum contracts and bloods flows out of the penis.

An erection is controlled by the nervous system. There are three neurotransmission pathways in the human body: the adrenergic nerves; the cholinergic nerves; and the non-adrenergic, non-cholinergic (“NANC”) nerves. The NANC nerves control erectile function. When a male human reacts to sexual stimuli, the NANC nerves send a signal to the penis. The neurotransmitter in this case is nitric oxide (“NO”).¹³ Thus, when the NANC nerves send a signal to the penis, they synthesize NO from L-arginine in the endothelial cells of the vascular system. The NO travels into the smooth muscle cells of the corpus cavernosum where it activates an enzyme known as guanylate cyclase. Guanylate cyclase synthesizes another enzyme, cyclic guanosine monophosphate (“cGMP”) by interacting with guanosine triphosphate. cGMP is the signaling enzyme that cues smooth muscle tissue, in this case the corpus cavernosum, to relax.¹⁴ This entire process is known as the L-arginine-nitric oxide-cyclic GMP pathway.

cGMP is a cyclic nucleotide, a form of enzyme. Enzymes, as is evident from cGMP's function in the smooth muscle described above, are proteins that catalyze chemical reactions in the body. cGMP is degraded by cGMP phosphodiesterase (“PDE”), another enzyme, which binds to cGMP and breaks it down into GMP. GMP does not have the same signaling effect in smooth muscle as cGMP. At the time the '012 patent was filed, there were five known types of PDEs: PDE1, PDE2, PDE3, PDE4, and PDE5. PDE1 and PDE5 both degrade cGMP and, thus, are termed cGMP PDEs.¹⁵

cGMP PDE can be inhibited by cGMP PDE inhibitors. An inhibitor functions in the same was that cGMP PDE itself functions with cGMP, by binding to it to block or decrease the activity of the enzyme. In other words, cGMP PDE inhibitors bind to cGMP PDE so that it, in turn, cannot bind to cGMP. The effectiveness of a PDE inhibitor is measured in terms of its potency, the amount of the inhibitor required to effectively inhibit the PDE,¹⁶ and its selectivity, i.e., the ratio at which the inhibitor prefers one PDE over another.¹⁷

B.

Beginning in 1985, Pfizer researchers in Sandwich, England were working on the creation of cGMP PDE inhibitor drugs to treat cardiovascular diseases such as hypertension and angina. Dr. Peter Ellis was the head of the team of biologists on the project, while Dr. Nicholas Terrett led the chemists. Pfizer hoped that cGMP PDE inhibitors would be able to treat these cardiovascular diseases by-causing relaxation of the smooth muscle tissue in the arteries, thereby lessening stress on the cardiovascular system. In particular, Pfizer aimed to create compounds that would inhibit cGMP PDEs, thereby enhancing the action of cGMP within smooth muscle and causing smooth muscle relaxation.

The project first started with the chemistry team creating compounds. Such compounds were based off other compounds known to inhibit cGMP PDE, and the chemistry team worked to make such compounds more selective, in terms of which enzyme they inhibited, and more potent in their inhibitory capability. ¹⁸ Once the compounds were made, the biology team tested the compounds in assays it designed to determine their selectivity and potency for cGMP PDE. The chemistry team then received feedback and modified the compounds further, if necessary, to improve their biological activity. The chemistry team also ran tests to assess the safety of the compounds, while the pharmacokinetic team studied the compounds to determine their absorption, distribution, metabolism, and excretion in the human body.

The chemistry team first synthesized sildenafil in 1989, and it quickly became a “lead compound,” after the biology and pharmacokinetic tests had been run.¹⁹ The results were so encouraging that the team working on the project recommended that Pfizer begin clinical development of sildenafil for the treatment of angina. See PTX 354. A year later, in July 1991, Pfizer began its first clinical trial using sildenafil, Study 201. Trial Tr. 695:21–697:14. As this clinical trial was a Phase I study, the subjects were healthy volunteers, in this case males, and the goal was to assess the safety of the drug and further determine its pharmacokinetic properties. This initial study, and several others after it, all tested single doses of sildenafil.

In 1992, Pfizer began a multiple dose study of sildenafil, again using healthy male volunteers, Study 207. Trial Tr....