Alza Corp. v. Mylan Laboratories, Inc.

• Decision Date: 27 September 2005
• Docket Number: No. CIV.A. 1:03CV61.,CIV.A. 1:03CV61.
• Citation: 388 F.Supp.2d 717
• Court: U.S. District Court — Northern District of West Virginia
• Parties: ALZA CORPORATION, Plaintiff, v. MYLAN LABORATORIES, INC. and Mylan Pharmaceuticals, Inc., Defendants.

388 F.Supp.2d 717

ALZA CORPORATION, Plaintiff, v. MYLAN LABORATORIES, INC. and Mylan Pharmaceuticals, Inc., Defendants.

No. CIV.A. 1:03CV61.

United States District Court, N.D. West Virginia.

September 27, 2005.

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COPYRIGHT MATERIAL OMITTED

Frank E. Simmerman, Jr., Simmerman Law Office, PLLC, Clarksburg, WV, Gregory L. Diskant, Jeb Harben, Jeffrey I.D. Lewis, Richard J. McCormick, Scott M. Brown, Patterson, Belknap, Webb & Tyler LLP, New York City, for Plaintiff.

Gordon H. Copland, Steptoe & Johnson, PLLC, Clarksburg, WV, James H. Wallace, Jr., John B. Wyss, Kevin P. Anderson, Kristin Yohannan, Robert J. Scheffel, Wiley Rein & Fielding LLP, Washington, DC, Roberta R. Wilson, Buchanan Ingersoll PC, Pittsburgh, PA, for Defendants.

POST-TRIAL MEMORANDUM OPINION AND ORDER

KEELEY, District Judge.

This is a patent infringement suit involving a pharmaceutical invention disclosed by U.S. Patent No. 6,124,355 (issued Sept. 26, 2000) ("the '355 patent"). The plaintiff, Alza Corporation ("Alza"), holds title to the '355 patent. The defendants in this case are Mylan Laboratories, Inc. and Mylan Pharmaceuticals, Inc. (collectively "Mylan").

Mylan committed acts of infringement by filing two Abbreviated New Drug Applications ("ANDAs") (Nos. 76-644 & 76-703) with the Food and Drug Administration ("FDA"), seeking permission to manufacture and distribute a generic version of an oxybutynin chloride extended-release tablet in 10 mg and 5 mg dosage forms, respectively. 35 U.S.C. § 271(e)(2). The ANDAs included a so-called "Paragraph IV" certification, which asserted that Mylan's products would not infringe the '355 patent and that the '355 patent is otherwise invalid. 21 U.S.C. § 355(j)(2)(A)(vii)(IV). As statutorily required, Mylan notified Alza of its ANDA filings. See id. §§ 355(j)(2)(B)(i)-(ii). Consequently, Alza filed this infringement action on May 2, 2003.¹

On December 7, 2004, the Court construed the disputed claims "according to [their] plain meaning and the parties' stipulated definitions" and denied Mylan's motions for summary judgment. Alza Corp. v. Mylan Labs., 349 F.Supp.2d 1002, 1021 (N.D.W.Va.2004). The Court subsequently held a ten day bench trial, which concluded on April 18, 2005. Thereafter, the parties filed extensive post-trial briefs.

Pursuant to Rule 52(a) of the Federal Rules of Civil Procedure, the Court now states its findings of fact and conclusions of law.² As discussed below, the Court concludes that Alza failed to meet its burden of proof with respect to its infringement claim and that the '355 is invalid as anticipated and obvious.

I. BACKGROUND

Claims 1, 2, 3, 11, 13 and 14 of the '355 patent are the subjects of dispute in the case at bar. These product and method claims disclose a sustained-release (or extended-release) version of oxybutynin, a drug used for the treatment of urinary incontinence since the 1970s. (J. Stip.¶ 34.) Before the invention of its sustained-release formulation, oxybutynin was administered two to four times a day to patients. '355 patent, col. 1:63-65. In contrast, the sustained-release formulation can be administered once a day because it delivers oxybutynin at a controlled rate over a 24 hour period. See id. at figs. 1 & 2.

Each asserted claim of the '355 patent recites a range of percentage or milligram amounts of oxybutynin that will be released within certain time intervals. In its claim construction, the Court determined that these ranges represent in vivo release rates, i.e., drug release in a human body. Alza, 349 F.Supp.2d at 1019. The Court also construed the asserted claims to encompass osmotic³ and non-osmotic⁴ dosage forms. See id. at 1010-11.

Mylan's ANDA product (or the "accused product") is a sustained-release oxybutynin formulation. Alza contends that the accused product releases drug within the claimed ranges of the '355 patent and thus infringes. Mylan denies infringement and affirmatively asserts several invalidity defenses, including inherent and express anticipation, inadequate written description, non-enablement and obviousness.

II. INFRINGEMENT

As the patentee, Alza bears the burden to show by a preponderance of the evidence that Mylan's product infringes the asserted claims of the '355 patent. Laitram Corp. v. Rexnord, Inc., 939 F.2d 1533, 1535 (Fed.Cir.1991). "The infringement inquiry is a two-step process. [A] court construes the disputed claim terms and then compares the properly construed claims to the accused device." Metabolite Laboratories, Inc. v. Laboratory Corporation Of America Holdings, 370 F.3d 1354, 1360 (Fed.Cir.2004) (citation omitted). "To literally infringe, the accused [product] must contain every limitation of the asserted claim." Texas Instruments Inc. v. Cypress Semiconductor Corp., 90 F.3d 1558, 1563 (Fed.Cir.1996) (citation omitted). Furthermore, "it is error for a court to compare in its infringement analysis the accused product or process with the patentee's commercial embodiment or other version of the product or process; the only proper comparison is with the claims of the patent." Zenith Labs., Inc. v. Bristol-Myers Squibb Co., 19 F.3d 1418, 1423 (Fed.Cir.1994) (citing Martin v. Barber, 755 F.2d 1564, 1567 (Fed.Cir.1985)); see also Corning Glass Works v. Sumitomo Elec. U.S.A., Inc., 868 F.2d 1251, 1262 (Fed.Cir.1989) ("The scope of a patent's claims determines what infringes the patent[.]") (quotation omitted).

In the case at bar, Mylan does not dispute that its accused product is a sustained-release oxybutynin formulation for oral administration to a patient containing a therapeutic dose of oxybutynin for treating incontinence. Therefore, Alza must prove that Mylan's 5 mg and 10 mg products satisfy each of the in vivo drug release limitations of the disputed claims. At trial, Alza did not elicit any scientific or testimonial evidence that establishes precise, numerical in vivo release rates for Mylan's accused product. Therefore, its infringement argument marshals evidence of (1) bioequivalence data from Mylan's accused product and Ditropan XL, and (2) in vitro testing of both drugs to estimate these release rates.

1. Bioequivalence Data Comparison

The first prong of Alza's infringement argument utilizes the results of Mylan's oxybutynin bioequivalence study,⁵ which compared the mean plasma concentrations of oxybutynin in the blood of subjects taking Ditropan XL and Mylan's accused product under fasted conditions. (See, e.g., DX 1581.) Alza maintains that these two sets of data "closely match" and demonstrate an "in vivo relationship between Ditropan XL and [the accused product] blood levels that is achieved only by infringement."

In asserting that Mylan's bioequivalence data demonstrates infringement, Alza presupposes that in vivo release rates of different dosage forms are equivalent, inasmuch as their plasma concentration levels are equivalent. The evidence, however, fails to support this critical postulate. Indeed, undisputed trial testimony indicates that bioequivalent drugs do not necessarily share the same in vivo or in vitro release rates. (Amidon Tr. at 976; Wargo Tr. at 1303-04.) Moreover, in its opening post-trial memorandum, Alza admits that "[b]ioequivalence data shows blood levels of drug, ... not release rates in the gastrointestinal tract. Accordingly, it is necessary to extrapolate backwards to derive useful information about release of the product." (Alza Post Trial Br. at 24) (emphasis in original).

Alza nonetheless argues that "in vivo bioequivalence data can be used to understand [the accused product's] in vivo release rate." (Id. at 25.) In this vein, it relies heavily on the testimony of Mylan's expert, Dr. Gordon Amidon. Alza maintains that, "as Dr. Amidon explained, the high permeability of oxybutynin means there should be almost an equivalence between release in the GI tract and the appearance in the blood." (Id.) (citing Amidon Tr. at 1109-11). Alza also quotes the following excerpt from Dr. Amidon's testimony:

Q. So the amount of drug that actually shows up in the blood is not the same as what is released in the GI tract, is that your —

A. Correct.

1. Q. But the profile of the amount that shows up in the blood would match with the profile of the amount that shows up, that is released; is that true?

A. Correct, yes.

(Amidon Tr. at 917-18.) The testimony cited by Alza confirms the obvious relationship between drug plasma levels and in vivo release rates. It does not, however, provide any objective and quantitative estimate of the accused product's in vivo release rates vis-a-vis the claimed release rates in the '355 patent.

In Alza's bioequivalence data analysis, the only "direct" evidence proffered to show the accused product's in vivo release rates is an excerpt from Dr. Amidon's testimony during cross examination. (Amidon Tr. at 1174-76.) To introduce this reference, Alza states that, "[a]s discussed with Dr. Amidon, [the accused product's in vivo] release follows line A on the curve [illustrated on PX 611]." (Br. at 34.) The identified exhibit, PX 611, graphically compares the results of in vitro dissolution tests on Ditropan XL and the accused product. Not surprisingly, "line A on the curve," which was drawn on the exhibit by Alza's counsel, neatly falls within the claimed release ranges of the '355 patent. (See PX 611.) As Mylan notes, however, Dr. Amidon rejected the very conclusion that Alza attributed to him with respect to the meaning of line A:

Q. Okay. So line A would be your best estimate of the in vivo release characteristic — excuse me, line A would be your best estimate of in vitro test results that would be predictive of Mylan's in vivo performance based upon your analysis of all of the data we talked about today, right?

A. No.

Q. I'm sorry?

A. No.

(Amidon Tr. at 1176.)

Otherwise, no expert endorsed Alza's subjective comparison of blood plasma levels with in vivo release rates. Therefore, considering the evidence...