Public & Experimental Use: Reduction to Practice Requires Knowledge that Invention Works for Intended Purpose

In re Omeprazole Patent Litigation (Fed. Cir. 2008)

The CAFC has affirmed a lower court trial finding that AstraZeneca’s Prilosec (omeprazole with an enteric coating and a subcoating) patents are infringed by the ANDA filings of Apotex, Torpharm, and Impax. (See U.S. Patent Nos. 4,786,505 and 4,853,230). This complex consolidated case has been handled by Judge Jones of the Southern District of New York. The case includes several important procedural issues, but here I focus on public use.

Public Use of a Pharmaceutical Formulation: Under 35 U.S.C. § 102(b), a patent will be considered invalid if the invention was “in public use” more than one year before the filing date. (i.e., before the “critical date”). The use in question was Astra’s large clinical trials used to test its omeprazole formulation. The district court ruled for Astra on two separate grounds: First that the clinical trials were an “experimental use” and therefore cannot qualify as public uses and second that the formulation was not yet ready for patenting until after the trials were completed.

Experimental Use and Reduction to Practice: In a series of cases over the past decade, the Federal Circuit has made clear that the experimental use defense “cannot negate a public use” that occurs after the invention is reduced to practice. At the same time, public use now requires proof that an invention is “ready for patenting” which generally requires reduction to practice (or at least being enabled to practice). For the most part, this rather new interpretation of public use subsumes the experimental use defense.

Here, the pills had been manufactured and were being used by clinical subjects. However, there were not “reduced to practice” because RTP requires knowledge “that the invention would work for its intended purpose.” On appeal, the Federal Circuit refused to overturn the lower court’s factual findings – instead agreeing the formulation was not reduced to practice because the company lacked experience of how it would perform clinically:

[Astra's expert witness] testified that as of May 1983 the Astra scientists did not have enough information to satisfy themselves that the Phase III formulation would work for its intended purpose. Instead, he testified that the Astra scientists thought the Phase III formulation “had a good possibility to be used as a marketing drug” but that the team did not have long-term stability data and had “no experience of how it performed in clinical studies.”

….

The Astra scientists had long understood that omeprazole could provide a safe and effective treatment for certain gastrointestinal diseases. The challenge they faced was developing a formulation to deliver omeprazole to the small intestine, a challenge that was made difficult by omeprazole’s sensitivity to acidic environments, such as the stomach. Impax has not demonstrated that, without conducting the Phase III clinical tests, the inventors knew that the Phase III formulation would achieve the goals of long-term stability and in vivo stability such that it would be effective as a treatment for gastrointestinal disease.

Because the efficacy of the formulation was not reduced to practice, its use could not be a public use.

Notes:

  • Of interest here is the idea that reduction to practice requires knowledge that the invention will work for its “intended purposes.” The specification of these patents detail the need for stability, so that purpose is clear. Because “purposes of the invention” have been used to limit claim scope, many modern patent applications don’t include such information. In those cases, will the purpose be found in extrinsic evidence?
  • The court here focused on reduction to practice to fulfill the “ready for patenting” prong of the public use analysis. Seemingly, the defendants may have had a better shot trying to show ready for patenting based on evidence that “prior to the critical date the inventor had prepared drawings or other descriptions of the invention that were sufficiently specific to enable a person skilled in the art to practice the invention.”

Zyprexa Patent Upheld on Appeal

OlanzapineEli Lilly v. Zenith Goldline (Fed. Cir. 2006)

Lilly’s patent covers olanzapine (Zyprexa®) and its use for the treatment of schizophrenia. Three generic manufacturers (Zenith (IVAX), Dr. Reddy’s, and Teva) filed an ANDA and Lilly responded with a complaint in the Southern District of Indiana.  After a bench trial, the district court agreed with Lilly that the patent was valid, infringed, and enforceable.  The defendants appealed to the Court of Appeals of the Federal Circuit.

Anticipation: To anticipate the invention, a prior art reference “must disclose each and every feature of the claimed invention, either explicitly or inherently.”  However, in both Petering and Schaumann, prior art references that disclosed the family of the claimed compound were found to anticipate the claimed compound — even though the claimed compounds were not specifically discussed.

Here, the CAFC found that those cases were not applicable because the closest reference to olanzapine did not spell out “a definite and limited class of compounds that enabled a person of ordinary skill in the art to at once envisage each member in this limited class.”

Obviousness: The CAFC agreed that the prior art references did not suggest a the compound. In addition, Lilly provided strong evidence of secondary considerations, including: “(1) a long-felt and unmet need; (2) failure of others; (3) industry acclaim; and (4) unexpected results.”

The record shows a long-felt need for a safer, less toxic, and more effective clozapine-like drug; a decade (or more) of failure to find a replacement for clozapine; a reasonable amount of commercial success for olanzapine; and a number of awards for olanzapine as indicators of industry acclaim.

Public Use: Prior to filing the patent application, Lilly conducted Phase I clinical safety trials. The court found, however, that the trials were well within the experimental use exception:

In this case, Lilly tailored its tests to their experimental drug safety and efficacy purpose, adequately monitored for results, and maintained confidentiality throughout the duration of the study. The trial court did not err in finding no public use.