By Donald Zuhn --
Last week, a divided panel of the Federal Circuit affirmed a determination by the District Court for the District of Delaware that the claims of U.S. Patent No. 4,663,318 were invalid for lack of enablement. The '318 patent, which issued on May 5, 1987 from U.S. Application No. 06/819,141, is directed to a method for treating Alzheimer’s disease with galanthamine. The lone independent claim of the '318 patent recites:
1. A method of treating Alzheimer's disease and related dementias which comprises administering to a patient suffering from such a disease a therapeutically effective amount of galanthamine or a pharmaceutically-acceptable acid addition salt thereof.
The majority opinion also notes that at the time the '141 application was filed, the small molecule galanthamine (at right; also known as galantamine) was known to inhibit acetylcholinesterase, an enzyme that breaks down acetylcholine. The majority opinion states that the specification for the '318 patent is "only just over one page in length" and provides "almost no basis for its stated conclusion that it was possible to administer 'an effective Alzheimer's disease cognitively-enhancing amount of galanthamine.'" The majority opinion also states that the specification provides "short summaries" of six scientific papers in which galanthamine had been administered to humans or animals, but "did not provide analysis or insight connecting the results of any of these six studies to galanthamine's potential to treat Alzheimer's disease in humans" or "refer to any then-existing animal test results involving the administration of galantamine in connection with this animal model of Alzheimer's disease."
During prosecution of the '318 patent, the examiner rejected the claims for indefiniteness and obviousness. In attempting to overcome the rejection, the inventor, Dr. Bonnie Davis, informed the Patent Office that "experiments [are] underway using animal models which are expected to show that treatment with galanthamine does result in an improvement in the condition of those suffering from Alzheimer's disease," and that it was "expected that data from this experimental work will be available in two to three months and will be submitted to the Examiner promptly thereafter." The majority opinion notes that the results of these experiments were not known until July 1987, after the '318 patent issued, that the studies "required several months and considerable effort by researchers at the Johns Hopkins University," and that the results were never submitted to the Patent Office. In November 1995, Dr. Davis licensed the '318 patent to Plaintiffs-Appellants Janssen Pharmaceutica N.V., Janssen L.P., and Synaptech, Inc. (Janssen).
In response, Janssen filed infringement suits against each ANDA filer. These infringement suits were consolidated.
Following a bench trial, the District Court determined that the '318 patent was invalid for lack of enablement. The District Court based its determination on two grounds: (1) the specification of the '318 patent did not demonstrate utility because relevant animal testing experiments were "not finished . . . by the time the '318 patent was allowed" and the specification provided only "minimal disclosure" of utility, and (2) the specification and claims did not "teach one of skill in the art how to use the claimed method" because the application "only surmise[d] how the claimed method could be used" without providing sufficient galanthamine dosage information.
Judge Dyk observes that "[t]ypically, patent applications claiming new methods of treatment are supported by test results," adding that "[o]ur predecessor court held in Krimmel [292 F.2d 948, 954 (CCPA 1961)] that animal tests showing that a new nonobvious compound 'exhibits some useful pharmaceutical property' are sufficient to demonstrate utility" and that "under appropriate circumstances, . . . the first link in the screening chain, in vitro testing, may establish a practical utility for the [pharmaceutical] compound in question," citing Cross v. Iizuka, 753 F.2d 1040, 1051 (Fed. Cir. 1985).
In affirming the District Court's judgment of invalidity for lack of enablement, Judge Dyk states that:
In this case, however, neither in vitro test results nor animal test results involving the use of galantamine to treat Alzheimer's-like conditions were provided. The results from the '318 patent's proposed animal tests of galantamine for treating symptoms of Alzheimer's disease were not available at the time of the application, and the district court properly held that they could not be used to establish enablement.
In addition, Judge Dyk notes that Janssen did not contend, either during prosecution or at trial, that the six scientific papers discussed in the specification of the '318 patent established utility. Instead, Janssen argued on appeal that utility may be established by analytic reasoning. In particular, Janssen argued that the specification "set forth the evidence from existing studies demonstrating galantamine's effects on central nicotinic as well as muscarinic receptors and connect[ed] it to a model for Alzheimer's therapy rendering those effects therapeutically relevant." Judge Dyk, however, states that "[t]hese insights . . . are nowhere described in the specification." He also states that "at the end of the day, the specification, even read in the light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis," which is "not sufficient." Judge Dyk, therefore, concludes that "[t]he '318 patent's description of using galantamine to treat Alzheimer’s disease thus does not satisfy the enablement requirement because the '318 patent's application did not establish utility."
Writing in dissent, Judge Gajarsa contends that District Court's determination of non-enablement should have been vacated because the lower court "did not undertake the required legal analysis to determine whether an ordinarily skilled artisan reading the patent would understand it to reveal a credible utility for the invention," and further, "failed to make the factual findings necessary to support the ultimate legal conclusion regarding enablement." Noting that "[t]he parties do not dispute that Dr. Davis's insight regarding galantamine's utility for treating Alzheimer's Disease (AD) was correct," Judge Gajarsa states that "[t]he relevant question here is whether, at the time Dr. Davis filed her application, the patent's written description would have credibly revealed to an ordinarily skilled artisan galantamine's utility for AD treatment."
With respect to the issues of obviousness and enablement, Judge Gajarsa argues that:
In terms of the present case, if Dr. Davis used her unique neuroendocrine perspective to examine the prior art and arrive at a novel insight about galantamine based on selected prior art findings, then the invention may be nonobvious; and if her patent disclosed those selected findings in such a manner that a person of ordinary skill would credit her insight regarding galantamine's utility, then the invention is enabled.
However, in the instant case:
[T]he district court committed error . . . by focusing generally on what the prior art does or does not teach -- the primary factual consideration underlying obviousness -- while neglecting to consider what the patent text discloses to an ordinarily skilled artisan -- the primary factual consideration underlying enablement.
In particular, Judge Gajarsa contends that the District Court failed to "determine how one of ordinary skill would understand [the findings of the six prior art studies described in the specification], either independently or in combination with one another."
Judge Gajarsa also finds fault with "the majority opinion's emphasis on the sufficiency of the evidence presented by Janssen." Stating that "the majority fails to establish the defendants' burden and instead focuses almost exclusively on the sufficiency of Janssen's showing and the merit of Janssen's arguments," Judge Gajarsa argues that such focus is improper. Moreover, "[b]ecause the district court erred as a matter of law and failed to make certain required factual findings," Judge Gajarsa contends that "we cannot defer to the district court's legal conclusion or fact-findings, and thus, it is particularly problematic for the majority to require Janssen to demonstrate on appeal that its patent is valid."