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Disclosed Ingestion of Loratadine Inherently Anticipates Claim to Metabolite Thereof

August 01, 2003
Troilo, Louis M.

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Last Month at the Federal Circuit - September 2003

Judges: Rader (author), Plager, and Bryson

In Schering Corporation v. Geneva Pharmaceuticals, Inc., No. 02-1516 (Fed. Cir. Aug. 1, 2003), the Federal Circuit affirmed a district court’s SJ of invalidity of certain claims of U.S. Patent No. 4,659,716 (“the ‘716 patent”) as being inherently anticipated.

U.S. Patent No. 4,282,233 (“the ‘233 patent“) discloses and claims the antihistamine loratadine, which is the active component of a pharmaceutical that Schering Corporation (“Schering”) markets as CLARITIN™. Schering’s subsequent ‘716 patent covers a metabolite of loratadine called descarboethoxyloratadine (“DCL”). Specifically, during the digestion process, the pharmaceutical undergoes a chemical conversion to form a new metabolite compound. Loratadine and its metabolite DCL structurally differ only in that loratadine has a carboethoxy group (-COOEt) on a ring nitrogen, whereas DCL has a hydrogen atom on that ring nitrogen. Unlike conventional antihistamines used at the time Schering launched CLARITIN™, both loratadine and its metabolite DCL are nondrowsy antihistamines.

The ‘233 patent issued on August 4, 1981, over one year before the earliest priority date of the ‘716 patent, and, thus, is prior art to the ‘716 patent under 35 U.S.C. § 102(b). While the ‘233 patent discloses and claims loratadine, it does not expressly disclose DCL or refer to metabolites of loratadine. Once the ‘233 patent expired, Geneva Pharmaceuticals, Inc. (“Geneva”) and the numerous other Defendants- Appellees sought to market generic versions of loratadine. In doing so, each Appellee sought regulatory approval and submitted an application to the FDA. After receiving notice of the FDA filings, Schering filed suit for infringement of the ‘716 patent. The parties filed cross motions for SJ on validity issues.

The district court construed claims 1 and 3 of the ‘716 patent to cover DCL in all its forms, including “metabolized within the human body” and “synthetically produced in a purified and isolated form.” Applying that construction, the district court found that the ‘233 patent did not expressly disclose DCL. However, the district court found that DCL was necessarily formed as a metabolite by carrying out the process disclosed in the ‘233 patent. Thus, the ‘233 patent inherently anticipated claims 1 and 3 of the ‘716 patent.

On appeal, Schering asserted that inherent anticipation requires recognition in the prior art. The Federal Circuit disagreed, observing that inherent anticipation does not require that a person of ordinary skill in the art at the time would have recognized the inherent disclosure. The Federal Circuit noted that DCL is not formed accidentally or under unusual conditions when loratadine is ingested. Rather, DCL necessarily and inevitably forms from loratadine under normal conditions as a necessary consequence of administering loratadine to patients. Therefore, despite the fact that skilled artisans did not recognize that the prior art ‘233 patent inherently produced DCL, and despite the fact that the ‘233 patent does not disclose any compound that is identifiable as DCL, the Court found inherent anticipation.

The Federal Circuit next examined whether Schering’s secret tests of loratadine before the critical date placed DCL in the public domain. According to Schering, DCL was not in the public domain such that it could be prior art against the ‘716 patent because Schering only tested loratadine in secret. The Federal Circuit disagreed, noting that anticipation does not require the actual creation or reduction to practice of the prior art subject matter; anticipation requires only an enabling disclosure. The Court thus ruled that actual administration of loratadine to patients before the critical date of the ‘716 patent was irrelevant. Rather, the ‘233 patent suffices as an anticipatory reference if it discloses in an enabling manner the administration of loratadine to patients.

Concerning whether the ‘233 patent contains an enabling disclosure of DCL, the Federal Circuit noted that this prior art patent need only describe how to make DCL in any form encompassed by a compound claim covering DCL, including DCL as a metabolite in a patient’s body. Because the ‘233 patent discloses administering loratadine to a patient, the inherent result of which is the formation of DCL metabolite, the Federal Circuit held that the ‘233 patent provides an enabling disclosure for making DCL.

The Federal Circuit noted that its conclusion on inherent anticipation does not preclude patent protection for metabolites of known drugs. Rather, the Court believed that with proper claiming, patent protection is available for such metabolites. For example, unlike the bare compounds recited in claims 1 and 3 of the ‘716 patent, the Court indicated that a metabolite may be claimed in its pure and isolated form, or as a pharmaceutical. Alternatively, the patent drafter could claim a method of administering the metabolite or the corresponding pharmaceutical composition. According to the Court, because the ‘233 patent does not disclose isolation of DCL, it does not provide an enabling disclosure to anticipate such claims. Applying this rationale to the ‘716 patent, claims 5-13 covering pharmaceutical compositions and claims 14- 16 covering methods of treating allergic reactions by administering compounds that include DCL were not found anticipated by the ‘233 patent.

Finally, the Federal Circuit upheld the district court’s finding that there was no genuine issue of material fact about whether ingestion of loratadine necessarily produces DCL metabolite. The Federal Circuit found that the district court’s conclusion was supported by extensive evidence, including thirteen clinical studies performed by Schering in which all 144 patients involved had measurable amounts of DCL in their systems after ingesting loratadine. This data conforms with Schering’s own expert, who testified that no human has been found that does not metabolize loratadine to DCL.