Claiming Metabolites: Federal Circuit Poses New Challenges to Patent Applicants
Warren D. Woessner Ph.D.
Patent Strategy & Management
09-30-2004
After they are administered, or taken by the patient, many drugs are converted into other chemical compounds or other physical forms, as the drugs are processed within the body of the patient. Often these compounds, known as metabolites, are the "active ingredient" that is responsible for the desired result, such as lowering blood pressure or cholesterol levels. The U.S. Court of Appeals for the Federal Circuit has also long recognized this effect and has held that the ingested form of a drug or its "metabolites" can be patented. Thus, an optimal patent strategy would require an inventor to patent both the pre-ingested form of the drug and its new physical forms or metabolites, as formed in the body ("in vivo"). However, the in vivo fate of the drug may not be learned until long after the "parent" drug has been tested and patented.
Two recent Federal Circuit decisions, Novartis Pharm. v. Eon Labs, 363 F.3d 1306 (Fed. Cir. 2004) and Schering Corp. v. Geneva Pharmaceuticals, Inc., 339 F.3d 1373 (Fed. Cir. 2003) will make it much more difficult for holders of "metabolite patents" to enforce them against accused infringers. In Novartis, the patent on the immunosuppression drug, cyclosporin, had expired, but Novartis had obtained a patent on an injectable "hydrosol" formulation of the drug. A hydrosol is a fine suspension, or colloid, of solid particles in a water-alcohol solution.
IN VIVO INFRINGEMENT ARGUED
Eon did not make or sell a hydrosol, but Novartis argued that the solution of cyclosporin that Eon did sell was converted into a hydrosol in the stomach of the patient. Since the patients were direct infringers, Novartis sued Eon for indirect infringement. The court framed the issue as whether "hydrosols," a term that appears in all the patent claim preambles, is limited to medicinal products prepared outside the body or whether it also includes products formed within the stomach of a patient after a particular medical product has been ingested.
To answer this question, the court reviewed dictionary definitions of "hydrosol." While the term was consistently defined, a number of the definitions referred to a dispersion of particles in a "solution." The court then located a definition of "solution" which included "an aqueous medical preparation with the solution ingredients soluble" in addition to the conventional definition, "a liquid containing a dissolved substance."
While the claims did not use the term "medical preparation," or even "solution," the court found that this definition introduced ambiguity into the meaning of the term "hydrosol," forcing it to turn to intrinsic evidence. Since the specification and prosecution history only referred to the claimed hydrosols in terms of medical preparations made outside the body, the court adopted the "narrower definition" of hydrosol, and summary judgment of noninfringement was affirmed.
DEFINITION FIRST -- DICTIONARY LATER?
This decision drew a stinging dissent from Judge Raymond C. Clevinger III, who criticized the majority's "dictionary expedition" in search of a definition which would support its holding. However, in the future, patent attorneys must be careful to avoid exclusive use of claim terms such as "formulation," "preparation" or other terms that remotely suggest processing outside of the body. Also, since both the majority and the dissent agreed that there is a "body of law that recognizes that medicinal preparations made in the body can infringe valid claims," specifications supporting claims to such mixtures should contain language that such mixtures are not excluded from the scope of some of the claims.
The second case, Schering Corp. v. Geneva, will make it more difficult for holders of "metabolite patents" to enforce them against accused infringers when the parent drug has been in use prior to the discovery and patenting of the metabolite. Schering had obtained a patent on the antihistamine loratidine, marketed as "Claritan®," and later obtained a patent that covered a metabolite of loratidine (DCL). Geneva sought to market a generic version of loratidine, and Schering sued for indirect infringement on the basis that DCL was inevitably formed in the stomachs of patients who ingested loratidine tablets. The district court held that the disclosure in the prior art loratidine patent of the administration of loratidine to patients inherently anticipated the later claims to the DCL metabolite, because it was necessarily formed when loratidine was taken.
A Federal Circuit panel of Judges Randall R. Rader, S. Jay Plager and William Curtis Bryson affirmed, but the refusal of the court to rehear the case en banc drew sharp dissents from both Judges Pauline Newman and Alan D. Lourie. The earlier loratidine patent did not disclose DCL or any other metabolites of loratidine, and the dissenters felt that the panel's blanket reliance on inherency deserved more careful scrutiny, especially since it appeared that one of skill in the art could not have recognized that DCL would be formed when loratidine is taken.
SUBMARINE SURFACING!
The Schering decision affirms the existence of a new class of submarine prior art that can invalidate patent claims on useful drugs that are obtained many years after the patent on the precursor drug has expired. The problem is not that "add-on" metabolite patents cannot now be enforced against those attempting to market generic forms of drugs that are "off-patent"; this bar may effectuate the earlier marketing of generic drugs. Rather, the issue of concern to the dissenters is the uncertainty engendered regarding the validity of patent claims to new drugs obtained by future researchers that are later found to be metabolites of "old drugs," when the prior art relating to the old drugs contained nothing to indicate that the "new drug" was formed when the old drug was administered. To safeguard against this threat, patent attorneys seeking patents to new drugs should always include claims to pharmaceutical compositions, preparations, doses or dosage forms and not simply rely on simple "compound" claims. It is clear from the recent decision of Novartis Pharm. Corp. v. Eon Labs that such claims will not be read to encompass metabolites formed in the body and should adequately protect new pharmaceutical products from anticipation by Schering-type prior art.
Warren D. Woessner Ph.D., is founding shareholder of Schwegman, Lundberg & Woessner, P.A. (www.slwk.com) in Minneapolis. His practice focuses on biotechnology and pharmaceutical patent law, including opinion work and advising clients on solutions to complex prosecution problems.
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