While the Supreme Court just granted certiorari in Myriad, case law surrounding the patent-eligibility of diagnostic and therapeutic personalized medicine has continued to develop in the wake of Mayo v. Prometheus. The good news for innovators is that the USPTO is still granting patents in the field of personalized medicine. The bad news is that the Federal Circuit is still invalidating claims as “indistinguishable” from those presented by Prometheus.
The USPTO Approach
Earlier this year, the USPTO issued examination guidelines for evaluating method claims under 35 USC § 101. The guidelines outline a three-step inquiry for examining claims that may fall under Prometheus:
- Is the claimed invention directed to a process, defined as an act, or a series of acts or steps?
If no, this analysis is not applicable. For product claims, see the Interim Examination Instructions for Evaluating Subject Matter Eligibility Under 35 U.S.C. § 101 issued August 24, 2009.
If yes, proceed to Inquiry 2. - Does the claim focus on use of a law of nature, a natural phenomenon, or naturally occurring relation or correlation (collectively referred to as a natural principle herein)? (Is the natural principle a limiting feature of the claim?)
If no, this analysis is complete, and the claim should be analyzed to determine if an abstract idea is claimed (see the 2010 Interim Bilski Guidance).
If yes, proceed to Inquiry 3. - Does the claim include additional elements/steps or a combination of elements/steps that integrate the natural principle into the claimed invention such that the natural principle is practically applied, and are sufficient to ensure that the claim amounts to significantly more than the natural principle itself? (Is it more than a law of nature + the general instruction to simply “apply it”?)
If no, the claim is not patent-eligible and should be rejected.
If yes, the claim is patent-eligible, and the analysis is complete.
The guidelines include a discussion of this framework and a list of factors that may be helpful in answering Inquiry 3. The guidelines emphasize consideration of the claim as whole, but indicate that “there must be at least one additional element or step that applies, relies on or uses the natural principle so that the claim amounts to significantly more than the natural principle itself.”
A method of analyzing a subject sample to identify at least a beginning of a kidney flare episode in a subject suffering from systemic lupus erythematosus (SLE), comprising:
i) assaying at least one urine sample from the subject for the amounts of hepcidin-20 and hepcidin-25, and
ii) characterizing the subject’s risk of having a kidney flare episode within about four months based upon the amounts of hepcidin-20 and hepcidin-25 measured in the at least one urine sample,
wherein the subject is characterized as being at risk of having a kidney flare episode within about four months when there is an increase in hepcidin-20 and a decrease in hepcidin-25 in the at least one urine sample, as compared to predetermined threshold levels. (Allowed June 2012)
A method for facilitating the diagnosis of a breast cancer in a subject, comprising detecting a fibrinogenαC domain polypeptide consisting of SEQ ID No. 1, from a blood sample from said subject, wherein a decrease of said polypeptide in said sample compared to a normal control sample indicates the presence of breast cancer in said subject. (Allowed July 2012)
A method of diagnosing a lipid storage disorder in a human subject, the method comprising:
obtaining a test sample from the subject;
determining the level of each of a group of biomarkers in the test sample, wherein the group of biomarkers includes 2,2′ di-22:6-BMP, 3,2′ di-22:6-BMP, 2,3′ di-22:6-BMP, and 3,3′di-22:6-BMP, and optionally includes di-22:6-PG, 2-mono-22:6-BMP, or 3-mono-22:6-BMP, and
comparing the level of each biomarker with a corresponding pre-determined level for the same biomarker, the pre-determined level being obtained from a control sample from a control subject who has the lipid storage disorder, wherein having a level of any of the group of biomarkers that is at or above the corresponding predetermined level indicates that the subject has or is at risk of developing the lipid storage disorder. (Allowed September 2012)
How the Federal Circuit Applied Prometheus in Myriad
The Federal Circuit applied Prometheus to the screening/diagnosing method claims in the Myriad patents. The court deemed claim 1 of U.S. Patent 5,709,999 to be representative:
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.
In its August 16. 2012 decision, the Federal Circuit held that these claims were invalid under 35 USC § 101 because they recite “nothing more than the abstract mental steps necessary to compare two different nucleotide sequences,” such as visually comparing the sequences. The court explained:
While “the application of a formula or abstract idea in a process may describe patent-eligible subject matter … Myriad’s claims do not apply the step of comparing two nucleotide sequences in a process. Rather, the step of comparing two DNA sequences is the entire process that is claimed.”
The court found that Myriad’s method claims at best were “indistinguishable from the claims the Supreme Court found invalid under § 101 in Mayo,” but noted that Myriad’s claims did not even recite a “determining” step that might invoke a transformative process.
How the Federal Circuit Applied Prometheus in PerkinElmer v. Intema
In a non-precedential opinion issued November 2012, the Federal Circuit determined that Intema’s diagnostic method claims were invalid under 35 USC § 101. The patent at issue was U.S. Patent 6,573,103 directed to prenatal screening methods for Down’s Syndrome. The court identified claim 1 as representative:
A method of determining whether a pregnant woman is at an increased risk of having a fetus with Down’s syndrome, the method comprising the steps of:
measuring the level of at least one screening marker from a first trimester of pregnancy by:
(i) assaying a sample . . . ; and/or
(ii) measuring at least one first ultrasound screening marker from an ultrasound scan . . .;
measuring the level of at least one second screening marker from a second trimester of pregnancy, the at least one second screening marker from the second trimester of pregnancy being different from the at least one first screening marker from the first trimester of pregnancy, by:
(i) assaying a sample . . .; and/or
(ii) measuring at least one second ultrasound screening marker from an ultrasound scan . . .; and
determining the risk of Down’s syndrome by comparing the measured levels of both the at least one first screening marker from the first trimester of pregnancy and the at least one second screening marker from the second trimester of pregnancy with observed relative frequency distributions of marker levels in Down’s syndrome pregnancies and in unaffected pregnancies.
(The district court had invalidated the claims on prior art grounds.)
The Federal Circuit cited Prometheus as setting forth the following analytical framework:
For a process claim to cover a patentable application of, for example, a natural law, it must “contain other elements or a combination of elements, sometimes referred to as an ‘inventive concept,’ sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself.” …. Process claims fail this requirement if, apart from the ineligible concept, they contain nothing more than “well-understood, routine, conventional activity previously engaged in by researchers in the field.” Because they merely describe the ineligible concept, amounting to a claim on the concept, such claims run afoul of section 101.
The court characterized Intema’s claims as reciting both “mental processes” and “natural laws”–two strikes under its § 101 analysis. The court considered if Intema’s claims added “enough” to satisfy § 101, but found that they did not:
The “measuring” steps were insufficient because “[t]hey merely tell the users of the process to measure the screening markers through whatever known method they wish.”
The “determining” steps were insufficient because they recite “the ineligible mental step of ‘comparing’ the measured markers “with observed relative frequency distributions … in Down’s syndrome pregnancies and in unaffected pregnancies.”
The claims as a whole did not fare any better because “anyone who wants to use this mental step or natural law must follow the claimed process.”
Further, the court noted that, like the claims at issue in Prometheus, ”there [was] no requirement that a doctor act on the calculated risk.”
More Guidance on a Case-By-Case Basis
While the Federal Circuit decisions in Myriad and Intema provide some guidance, neither address the difficult questions that arise when applying Prometheus and/or the USPTO’s examination guidelines to methods that involve more specific, concrete and unconventional steps. We will have to wait for more decisions from the Federal Circuit–and the Supreme Court–before we can mark the boundaries of patent-eligibility with any certainty.