by Jake Meyer

Recently the Federal Circuit ruled on the case Prometheus Labs, Inc. v. Mayo, a case involving 35 U.S.C. §101 subject matter.  Prometheus came before the Federal Circuit as an appeal from a decision from the United States District Court for the Southern District of California to grant summary judgment of invalidity of Prometheus’s patents (U.S. Patents 6,355,623 and 6,680,302) finding that the claims were directed to non-statutory subject matter.   The case was a little unusual in that it was decided by two Federal Circuit judges, Michel and Lourie, and District Court Judge — Judge Clark of the United States District Court for the Eastern District of Texas.  The patents claim methods for calibrating the proper dosage of thiopurine drugs, which are used for treating autoimmune diseases.  Since the patents are directed to a process and the case involves a subject matter inquiry, the Federal Circuit was able to revisit In re Bilski (a case now before the Supreme Court) and apply the test for subject matter eligibility of a process the Federal Circuit laid out in Bilski.

Thiopurine drugs are used to treat inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.  Thiopurine drugs include 6-mercaptopurine (6-MP), and azathiopurine, which upon administration to the patient converts to 6-MP.  The body breaks down 6-MP into different metabolites, such as 6-methyl-mercaptopurine (6-MMP) and 6-thioguanine (6-TG).  Prometheus’s patents involve the measurement of these metabolites.  For example, claim 1 of patent 6,355,623 is representative of the claims in the Prometheus:

1. A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:
(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and
(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder,
wherein the level of 6-thioguanine less than about 230 pmol per 8.times.10.sup.8 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and
wherein the level of 6-thioguanine greater than about 400 pmol per 8.times.10.sup.8 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

So the claims involve two steps: 1) "administering" a drug that results in a certain metabolite in the person’s body, and 2) "determining" the level of the metabolite.  The measured metabolite levels are then compared to pre-determined metabolite levels and the measured metabolite levels "indicate a need" to increase or decrease the level of the drug.

Relying on its discussion in Bilski, the Federal Circuit explained that "[t]he key issue for patentability, then, at least on the present facts, is whether a claim is drawn to a fundamental principle or an application," where a fundamental principle is "i.e., a law of nature, natural phenomenon, or abstract idea."  The Federal Circuit then reiterated that it had "articulated in Bilski a 'definitive test' for determining whether a process is patent-eligible under §101:  'A claimed process is surely patent-eligible under §101 if: (1) it is tied to a particular machine or apparatus, or (2) it transforms a particular article into a different state or thing.'"  There are also two other requirements of the test: "the use of a specific machine or transformation of an article must impose meaningful limits on the claim’s scope to impart patent-eligibility," and "the involvement of the machine or transformation in the claimed process must not merely be insignificant extra-solution activity."  "The transformation must be central to the purpose of the claimed process."

The Federal Circuit concluded in Prometheus that the methods of treatment claimed in the patents are patentable subject matter because they a "'transform an article to a different state or thing,' and this transformation is 'central to the purpose of the claimed process.'"  The court found that the transformation was of the human body after the drug is administered and the chemical and physical changes of the drug's metabolites which allow the metabolite levels to be determined.  The court stated that the "asserted claims are in effect claims to methods of treatment, which are always transformative when a defined group of drugs is administered to the body to ameliorate the effects of an undesired condition." 

The court also found the "determining" step to be transformative.  Determining metabolite levels involves a transformation because they "cannot be determined by mere inspection.  Some form of manipulation, such as high pressure liquid chromatography method . . . or other modification of the substances to be measured, is necessary to extract the metabolites from a bodily sample and determine their concentration."  And it is this chemical or physical transformation on a physical substance that "sufficiently confines the patent monopoly, as required by Bilski."

The court did not view the claims as claiming natural correlations or data-gathering steps. The court viewed the administration step as transformative and therefore not a data-gathering step.  "The transformation here, however, is the result of the physical administration of a drug to a subject to transform—i.e., treat—the subject, which is itself not a natural process."  The court found the steps to be not to be "merely" for the purpose of gathering data, but instead are part of a treatment protocol.

The court did agree with the district court that the "wherein" clauses are mental steps.  The "wherein" clause of claim 1 of patent '623 involves the indication to increase or decrease the dosage of the drug based on the "determined" metabolite level.  This claim could be infringed by a doctor measuring a patient’s metabolite level and thinking "oh, I should adjust the drug dosage, because this dosage is toxic to the patient."  The court stated, however, that "a subsequent mental step does not, by itself, negate the transformative nature of prior steps," and that this mental step did not make Prometheus’s claims unpatentable. 

The Federal Circuit's treatment of the "wherein" clause ignores both a doctrine of patent law.  First, the U.S. Supreme Court has held that mental steps are not patentable.  The Federal Circuit stated that this subsequent mental step does not make the transformative steps unpatentable, but does not mention that this clause is unpatentable and should be unenforceable.  The Federal Circuit should have either stated that the "wherein" clause is unenforceable or deleted the clause all together.  Based on this decision, the "wherein" clause is still part of this claim and therefore a mental step is patented.  The conflicts with patent law doctrine and prevents physicians from thinking about this correlation between metabolite levels and adjusting drug dosage.

Ultimately, the Federal Circuit should not have considered these claims to be transformative.  The patentee did not invent a new drug, nor are the claims directed to a new drug.  The "administering" step, which the Federal Circuit considered transformative, relies on the bodies natural processes.  The metabolite levels are the result of the bodies' natural reaction to these drugs.  In fact, these natural processes are predictable enough in the human body, that one can determine effectiveness and toxicity of the drug based on these metabolite levels.  Neither is the determinative step transformative.  The determining step is as transformative as "determine m," "determine c," wherein E=mc2.  Determining variables in an equation or metabolite levels in the body and correlating them are not transformative.  Nor are they "central to the purpose of the claimed process."  The drug metabolite levels and their implications for the human body (effectiveness of drug and toxicity) are "central to the purpose of the claimed process," and they are a natural phenomenon.  Further, the determining step involves measurements using non-innovative steps, as these methods for determining metabolite levels existed prior to this patent.

Prometheus mechanically follows the machine-or-transformation test laid out in Bilski to determine the patentability of a process.  This case illuminates what the Federal Circuit considers to be transformative in biotechnology.  According to the Federal Circuit, administering a drug is transformative as is testing for metabolite levels as long as it involves any physical step.  The Court will have to opportunity in In re Bilski to determine whether the machine-or-transformation test is the "definitive" test for determining subject matter eligibility for a process claim or at least provide guidance to the Federal Circuit as to what is to be considered transformative.  And considering that United States Supreme Court precedent does not allow the patenting of natural phenomenon and mental processes, the Court may decide this test — which finds claims to the administration of a drug and measuring of metabolite levels to be patentable — to be an unworkable test.