Alza Corp. v. Andrx Pharmaceuticals, LLC

• Decision Date: 26 April 2010
• Docket Number: No. 2009-1350.,2009-1350.
• Parties: ALZA CORPORATION and McNeil-PPC, Inc., Plaintiffs-Appellants, v. ANDRX PHARMACEUTICALS, LLC and Andrx Corporation, Defendants-Appellees.
• Court: U.S. Court of Appeals — Federal Circuit

603 F.3d 935

ALZA CORPORATION and McNeil-PPC, Inc., Plaintiffs-Appellants, v. ANDRX PHARMACEUTICALS, LLC and Andrx Corporation, Defendants-Appellees.

No. 2009-1350.

United States Court of Appeals, Federal Circuit.

April 26, 2010.

Constantine L. Trela, Jr., Sidley Austin LLP, of Chicago, IL, argued for plaintiffs-appellants. With him on the brief were David T. Pritikin; Jeffrey P. Kushan, Todd A. Wagner and Peter S. Choi, of Washington, DC.

C. Kyle Musgrove, Kenyon & Kenyon LLP, of Washington, DC, argued for defendants-appellees. With him on the brief were John W. Bateman and Robert F. Vroom.

Before DYK, SCHALL, and PROST, Circuit Judges.

PROST, Circuit Judge.

ALZA Corporation and McNeil-PPC, Inc. (collectively, "ALZA") appeal from a final decision of the United States District Court for the District of Delaware. Following a bench trial, the district court found the patented treatment methods of U.S. Patent No. 6,919,373 ("'373 patent") nonobvious, but held the asserted claim both not infringed and invalid for lack of enablement. We affirm because we conclude that the asserted claims of the '373 patent are invalid for lack of enablement.

BACKGROUND

The '373 patent claims methods for treating primarily Attention Deficit and Hyperactivity Disorder ("ADHD") through a methylphenidate ("MPH") drug dosage form that has an ascending release rate over an extended period of time. The '373 patent application, filed in 1999, claimed priority to provisional application No. 60/031,741 ("'741 application"), filed on November 25, 1996, and the earliest nonprovisional application No. 08/910,593 ("'593 application"), filed on July 31, 1997.

Before the claimed invention, ADHD had been treated with other oral drugs, the most common of which, Ritalin®, was an immediate-release ("IR") formulation of MPH. This formulation releases the drug within minutes and treats the symptoms for three to five hours. As a result, such prior drug treatments were taken two or three times a day. As many patients who take ADHD medication are children, they took one dose before school and one or two additional doses about four to five hours apart, at least one of which was administered at school. Thus, a once-a-day method of treating ADHD offered the potential of reducing patient-compliance problems that resulted from the need for treatment during the school day.

At the time of the invention, it was well known how to develop sustained-release dosage forms, also known as "controlled release" or "extended release." Designed to release the drug at a constant rate, sustained-release dosage forms typically provided the desired steady therapeutic effect. It was also known that sustained-release dosage forms could exhibit descending or ascending release rates by manipulating the methods and materials used to produce the dosage forms.

After a series of clinical studies, ALZA determined that MPH plasma concentrations that had ascending patterns provided greater efficacy for treating ADHD than concentrations that were constant. Using this knowledge, ALZA developed safe and effective once-a-day extended release oral dosage forms that could deliver MPH with the ascending release pattern. Admittedly, the bulk of ALZA's efforts went into developing an osmotic dosage form, which uses a compartment containing drug and various osmotic excipients.

ALZA subsequently filed its patent applications. Claim 1, the only independent claim implicated on appeal, of the '373 patent claims:

A method for treating ADD or ADHD comprising administering a dosage form comprising methylphenidate that provides a release of methylphenidate at an ascending release rate over an extended period of time.

'373 patent col.23 ll.12-15 (emphasis added). The specification focuses on how osmotic systems can be adapted to create an ascending release dosage form to treat ADHD. The specification also mentions non-osmotic dosage forms. Id. at col.3 ll.53-62.¹

ALZA markets and sells a product called CONCERTA®, which embodies the claimed invention; upon ingestion, it releases the drug at an ascending rate for an extended period of time, as required by claim 1. ALZA's competitors, Andrx Pharmaceuticals, LLC and Andrx Corporation (collectively, "Andrx"), produce a product pursuant to an approved Abbreviated New Drug Application ("ANDA"). Like CONCERTA®, Andrx's product has an outer IR coating around a sustained-release inner core. In 2005, ALZA sued Andrx, alleging infringement of the '373 patent and U.S. Patent No. 6,930,129 ("'129 patent").² Andrx denied that its products infringed the patents. It also asserted affirmative defenses, alleging that the '373 patent was invalid because it was obvious and not enabled, and counterclaimed for a declaratory judgment of noninfringement and invalidity of the asserted claims of the '373 patent.

The district court held a Markman hearing on the construction of various terms in dispute. In rejecting Andrx's attempt to limit the scope of the claim to osmotic dosage forms, the court construed the phrases "pharmaceutically acceptable composition" and "dosage form" to mean "a pharmaceutical composition that includes a dose of methylphenidate," which includes non-osmotic dosage forms, as ALZA requested.³ Alza Corp. v. Andrx Pharms., LLC, No. 05-642, at 2 (D.Del. Oct. 5, 2007) (order on claim construction). Further, the court construed the disputed term "an ascending release rate over an extended period of time" to mean:

a release of methylphenidate from the dosage form wherein the amount released in a periodic interval is increased over the amount released during the immediately preceding periodic, interval starting at t=0 and continuing through at least the mid-point of the T90 and for at least three hours. The release rate is determined by an appropriate in-vitro dissolution test. The ascending release rate does not include release of drug from any immediate-release drug coating that may be applied to the dosage form.⁴

Id.

Following a bench trial, the district court determined that the '373 patent was not infringed. The district court concluded that claim 1, as construed, "requires release of non-IR MPH during the initial interval of an appropriate dissolution test." Alza, 607 F.Supp.2d at 624. According to the district court, there was substantial evidence that "the amount of MPH released by Andrx's product in the first hour of the dissolution test is all attributable to the IR portion of methylphenidate," which ALZA failed to adequately rebut. Id. at 628-31. The district court also found the asserted claims of the '373 patent not obvious.

The district court, however, concluded that the asserted claims are invalid for lack of enablement because the specification does not enable the full scope of claim 1, which covers both osmotic and non-osmotic dosage forms. Before the district court, the parties agreed that the specification enables osmotic oral dosage forms, but disputed whether it also enables non-osmotic oral dosage forms. While the court found that the claim includes non-oral as well as oral dosage forms, it concluded that it could resolve the enablement dispute between the parties in Andrx's favor solely by looking to non-osmotic oral tablets and capsules. As a result, it explained that the enablement issue reduces to factual considerations with regard to whether undue experimentation is required to make oral dosage forms other than osmotic dosage forms that meet the limitations of the claims. Applying the factors set forth in In re Wands, 858 F.2d 731, 735 (Fed.Cir.1988),⁵ the district court found that developing non-osmotic oral dosage forms, such as tablets and capsules, as claimed requires undue experimentation. Alza, 607 F.Supp.2d at 651-59. Accordingly, the district court determined that the asserted claims are not enabled and thus invalid.

ALZA timely appeals. We have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).

DISCUSSION

On appeal, ALZA argues that the district court erred in finding claim 1 invalid for lack of enablement. The parties agree that the claim construction adopted by the district court requires the enablement of both osmotic and non-osmotic dosage forms and they also agree that osmotic dosage forms are enabled. The dispute is whether the specification would have enabled a person of ordinary skill in the art to create non-osmotic oral dosage forms — namely, tablets and capsules — with ascending release rates without undue experimentation at the time of filing.⁶

ALZA asserts that creating non-osmotic dosage forms and manipulating their release rates was well known to a person of ordinary skill in the art at the time the '373 patent application was filed. In addition, ALZA argues that the specification provides sufficient guidance regarding non-osmotic dosage forms because it identifies a variety of suitable non-osmotic dosage forms and cites to a portion of a standard text to explain how to make and use such non-osmotic, sustained-release dosage forms with experimentation. ALZA concedes that even with the guidance provided in the specification, a person of ordinary skill in the art would be required to engage in an iterative, trial-and-error process to practice the claimed invention; however, it disputes that the amount of experimentation required is undue. Instead, ALZA argues that non-osmotic dosage forms with ascending release rates could be made with only routine effort by those skilled in the art because the methods and materials used to produce dosage forms with constant, descending, or ascending release rate profiles are essentially the same and well known.

Andrx disputes ALZA's contention that enablement can be satisfied by referring to what persons of ordinary skill would know because what one of the proper skill in the art knows cannot substitute for disclosure of novel aspects of the invention, i.e., the non-osmotic dosage forms exhibiting ascending release rates. Further, Andrx argues that the...