Even for patent attorneys who specialize in personalized medicine, confusion still exists as to the best way to pursue and enforce diagnostic method patent claims in light of patent eligibility considerations under 35 U.S.C. §101.  While the Supreme Court and Federal Circuit have provided some guidance regarding patent eligibility of certain method claims, details of how to proceed when drafting relevant claims, and which existing diagnostic method claims are viable, remain unclear to many.

It is possible that the Federal Circuit and/or Supreme Court may provide additional direction in cases yet to be decided.  Such cases include the AMP et al. v. USPTO et al. (Myriad) “gene patenting” case (pending at Federal Circuit after oral argument on April 4, 2011), Classen Immunotherapies v. Biogen IDEC (pending at the Federal Circuit after remand by the Supreme Court in 2010) and Prometheus Labs., Inc. v. Mayo Collaborative Servs. (awaiting decision by Supreme Court on certiorari petition-again).

In the meantime, patent attorneys glean what they can from cases decided before and after Bilski v. Kappos (2010), such as In re Grams (Fed. Cir. 1989), Justice Breyer’s dissent from dismissal of the grant of certiorari in Lab. Corp of America Holdings v. Metabolite Labs., Inc. (2006), as well as the most recent Federal Circuit decision in Prometheus Labs., Inc. v. Mayo Collaborative Servs. (Fed. Cir. 2010) (albeit cert. pending at Supreme Court).

While such pending and decided cases are not an exhaustive list of ones that may impact patent eligibility of diagnostic method claims, it is informative to look at claims at issue in these cases.  Below provides a brief summary of representative claims, and what the courts have said about them so far.

  • In re Grams, 888 F.2d 835 (Fed. Cir. 1989) (patent ineligible)

Claim 1 of U.S. Application Ser. No. 625,247:

1. A method of diagnosing an abnormal condition in an individual, the individual being characterized by a plurality of correlated parameters of a set of such parameters that is representative of the individual’s condition, the parameters comprising data resulting from a plurality of clinical laboratory tests which measure the levels of chemical and biological constituents of the individual [sic] and each parameter having a reference range of values, the method comprising

[a] performing said plurality of clinical laboratory tests on the individual to measure the values of the set of parameters;

[b] producing from the set of measured parameter values and the reference ranges of values a first quantity representative of the condition of the individual;

[c] comparing the first quantity to a first predetermined value to determine whether the individual’s condition is abnormal;

[d] upon determining from said comparing that the individual’s condition is abnormal, successively testing a plurality of different combinations of the constituents of the individual by eliminating parameters from the set to form subsets corresponding to said combinations, producing for each subset a second quantity, and comparing said second quantity with a second predetermined value to detect a non-significant deviation from a normal condition; and

[e] identifying as a result of said testing a complementary subset of parameters corresponding to a combination of constituents responsible for the abnormal condition, said complementary subset comprising the parameters eliminated from the set so as to produce a subset having said non-significant deviation from a normal condition.

In this 1989 decision on appeal from the USPTO Board of Patent Appeals and Interferences, the Federal Circuit determined that the essence of the claimed process was a mathematical algorithm, and not any transformation of the tested individuals.  The court concluded the process was merely an algorithm combined with a data-gathering step, i.e., performing a clinical test.  The claims did not require the performance of clinical tests on individuals that were transformative.  Instead, the tests simply obtained data.

Claim 13 of U.S. Patent No. 4,940,658:

13.  A method for detecting a deficiency of cobalamin or folate in warm-blooded animals comprising the steps of:

assaying a body fluid for an elevated level of total homocysteine; and

correlating an elevated level of total homocysteine in said body fluid with a deficiency of cobalamin or folate.

This pre-Bilski decision may provide insight into the thinking of at least some Supreme Court Justices, especially after the Court said nothing when remanding Prometheus and Classen in light of Bilski (a case relating to business method claims, not diagnostics).  In this opinion, Justice Breyer (joined by Justices Stevens and Souter) found that claim 13 was “not a process for transforming blood or any other matter,” but rather “instructs the user to (1) obtain test results and (2) think about them.”  The fact that the assaying step involved the transformation of blood through an unpatented procedure was unavailing.

The three Justices concluded that the claim failed the requirement “that it not amount to a simple natural correlation, i.e., a natural phenomenon.”  As stated in the opinion, the claim here “simply describes the natural law at issue in the abstract patent language of a ‘process,'” and the patentee  “cannot avoid the fact that the process is not more than an instruction to read some numbers in light of medical knowledge.”  Aside from an unpatentable assaying step, claim 13 recited only the correlation between the homocysteine and vitamin deficiency that the researchers uncovered.  As stated by Justice Breyer, “[i]n my view, that correlation is an unpatentable “natural phenomenon,” and I can find nothing in claim 13 that adds anything more of significance.”

Claim 1 of U.S. Patent No. 6,355,623:

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 8×108 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 8×108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

Claim 46 of the U.S. Patent No. 6,680,302:

46. A method of optimizing therapeutic efficacy and reducing toxicity associated with treatment of an immune-mediated gastrointestinal disorder, comprising:

(a) determining the level of 6-thioguanine or 6-methylmercaptopurine in a subject administered a drug selected from the group consisting of 6-mercaptopurine, azathiop[u]rine, 6-thioguanine, and 6-methyl-mercaptoriboside, said subject having said immune-mediated gastrointestinal disorder,

wherein the level of 6-thioguanine less than about 230 pmol per 8×108 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 8×108 red blood cells or a level of 6-methylmercaptopurine greater than about 7000 pmol per 8×108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

In this post-Bilski decision, the Federal Circuit held that both the “administering” and “determining” steps were transformative and not merely data-gathering steps.  Specifically, the method claims recited a patent-eligible application of naturally occurring correlations between metabolite levels and efficacy/toxicity, i.e., the treatment of a specific disease by administering specific drugs and measuring specific metabolites.  As noted by the court, “[t]he invention’s purpose to treat the human body is made clear in the specification and the preambles of the asserted claims.”  Thus, the method did not wholly preempt all uses of the recited correlations.  The methods were not “merely” data-gathering steps or “insignificant extra-solution activity,” but rather were part of treatment regimes, and therefore involved “a significant transformative element.”

Claim 1 of U.S. Pat. No. 5,709,999:

1. A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human which comprises

analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or

analyzing a sequence of BRCA1 cDNA made from mRNA from said human sample with the proviso that said germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1.

Claim 1 of U.S. Pat. No. 5,753,441:

1.  A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises

comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject.

Claim 20 of U.S. Pat. No. 5,747,282:

20. A method for screening potential cancer therapeutics which comprises:

growing a transformed eukaryotic host cell containing an altered BRCA1 gene causing cancer in the presence of a compound suspected of being a cancer therapeutic,

growing said transformed eukaryotic host cell in the absence of said compound,

determining the rate of growth of said host cell in the presence of said compound and the rate of growth of said host cell in the absence of said compound and comparing the growth rate of said host cells,

wherein a slower rate of growth of said host cell in the presence of said compound is indicative of a cancer therapeutic.

While DNA composition claims in Myriad gets much attention because they potentially relate biotechnology patent estates overall (and certainly personalized medicine IP), method claims at issue in this case are also worth noting.  Arguments on both sides regarding these method claims may spur the Federal Circuit to provide more insight regarding patent eligibility of diagnostic claims that differ from those at issue in Prometheus.

  • Classen v. Biogen, 304 Fed. Appx. 866 (Fed. Cir. 2008) (patent ineligible) (pending at Federal Circuit again after remand from Supreme Court after Bilski in 2010)

Claim 1 of U.S. Pat. No. 5,723,283:

1. A method of determining whether an immunization schedule affects the incidence or severity of a chronic immune-mediated disorder in a treatment group of mammals, relative to a control group of mammals, which comprises

immunizing mammals in the treatment group of mammals with one or more doses of one or more immunogens, according to said immunization schedule, and

comparing the incidence, prevalence, frequency or severity of said chronic immune-mediated disorder or the level of a marker of such a disorder, in the treatment group, with that in the control group.

While Prometheus has garnered more attention, the Federal Circuit has not yet issued a decision in Classen, a case remanded in 2010 on the same day as Prometheus in light of Bilski.  According to public record, parties in Classen filed supplemental briefs with the Federal Circuit in October 2010, and presumably the case is still live.  Again, because the claims here differ from those in Prometheus, it is possible that the Federal Circuit could use this case to provide additional insight into exactly what types of diagnostic methods are (or are not) patent eligible.