On Oct. 17^th, the PTO published Guidelines intended to supplement the Jan. 2019 Subject Matter Eligibility Guidelines (“2019 PEG”). The Guidelines and associated Examples are extensive. Only two of the Examples (43 and 44) are concerned with the life sciences. Example 43 is a method of medical treatment claim and 44 is a claim to a packaged natural product, that contains the natural product in a self-injectable patch to control diabetes, or combines it with another natural product.

Diagnostic method claims per se and the role of naturally-occurring correlations are not directly discussed, although there is a statement that naturally-occurring relationships recited in claims and laws of nature. Here are claims 1 and 3 of Example 43:

1. A treatment method comprising:

   1. calculating a ratio of C11 to C13 [protein]  levels measured in a blood sample from a patient diagnosed with NAS-3 [a kidney disease] to identify the patient as having a non-responder [to first-line steroid treatment] phenotype;

   2. administering a treatment to the patient having a non-responder phenotype.

2. The method of claim 1 where the treatment is rapamycin.

The Guidelines spend 6 pages discussing claims 1-5, which you should read for yourself in any case. I will just discuss some points of interest. Step (a) looks like a truncated diagnostic claim. The blood sampling and marker level measurement steps have already taken place outside of the four corners of the claim; only the ratio calculation step remains in step (a). We are not told if applicants discovered the protein. While a calculated ratio of greater than 3 identifies a non-responder, who will receive a non-steroidal second line treatment, the ratio is not recited in the claim. The PTO seems to be distancing itself from claims like the ones being appealed in Myriad.

The Guidelines confirm that Step 2A of the Mayo/Alice test now has two prongs: (1) Does the claim “recite” a judicial exception to patent eligibility (PE) and (2) Do the rest of the claim elements “integrate the judicial exception into a practical application.” In this case claim 1 recites calculating a ratio of markers which is called a mathematical calculation. Because it could be performed wholly by the human mind, the claim also recites a mental process. These are both subcategories of “abstract idea.” The claim is also asserted to recite a law of nature – the naturally occurring relationship between the ratio and the phenotype of the patient (responder or non-responder). The words “correlation” and “diagnosis” do not appear.

Claim 1 is found patent ineligible, despite the treatment step. Because the treatment element is too broad to integrate the exception(s) into a practical application of the natural law in step (a). I have problems with the step (b) analysis in the Guidelines, but at least one thing is clear – the diagnosis step is not a practical application of the exception(s)—it is one of the exceptions! Later Ambry is cited as holding that comparing a test value to a standard is a mental process.

To return to the step (b) analysis, despite the recitation in the claim that the non-responders are “treated”, the Guidance says that the claim does not require a doctor to take the calculation step’s outcome, the patient’s phenotype, into account when deciding which treatment to administer, part of the rationale of the S. Ct.’s Prometheus v. Mayo decision.

This is just wrong. The selected non-responders would be treated differently than the responders. At page 2, lines 1-2, the Guidance states that the ratio of the markers would lead to “subsequently adjusting treatment in accordance with the calculation, [and] contribute to optimal treatment and better clinical outcomes for NAS-3.” The PTO is pushing too hard to make this claim resemble the facts in Mayo, which did not recite treating a patient.

Not surprisingly, claim 3 is found to be patent-eligible. Part (a) of the claim still contains 2-3 judicial exceptions, but under Step 2B of the Mayo/Alice rule, the claim elements are considered in combination, and the conventionality of the treatment step is not considered. Now the PTO takes the position that the judicial exception(s) – calculating the ratio of the marker proteins and using it to identify non-responders– an abstract idea, leads to a treatment that is particular to that identified phenotype.

Endo and Vanda are cited as both using a judicial exception to identify patient in need of a particular treatment and then administering the particular treatment to the identified patients.

Claim 44 is based on the inventors’ discovery that a compound, Denvertic Acid, is present in the bark of The Rocky Mt. cassia tree, and that it is a “short acting agent” useful for glycemic control in diabetic patients. The claims follow:

1. A dosage unit comprising denveric acid in a container.

2. The dosage unit of claim 1 wherein the container is a wearable delivery {patch that delivers the acid from a reservoir via a needle assembly].

3. The dosage unit of claim 1 wherein the denveric acid is an intermediate-acting  [sustained action] denvaric acid.

4. The dosage unit of claim 1, further comprising protamine [another natural product] that is mixed with the denvaric acid in a container in an amount of 0.75 mg to 1.5 mg protamine per every mg of denvaric acid [ This mixture exhibits long-acting glycemic control].

Not surprisingly, claim 1 was found to be patent-ineligible. The denveric acid in the container does not exhibit markedly difference characteristics from the naturally occurring acid. While the “markedly different” test is taken from the Chakrabarty decision, that decision involved a transgenic bacterium. While the PTO has extended this requirement to all products of nature, the Federal Circuit has not clearly ruled on the patentability of non-living organisms. The Roslin decision involved cloned sheep. The PTO mischaracterizes Myriad as holding that “naturally occurring things are ‘products of nature’ which cannot be patented.” The Myriad holding was limited to isolated genes and naturally occurring fragments thereof.

As patent attorneys, we should observe a moment of silence for Bergy II, a decision written by Judge Rich, in which the CCPA held that claims to “a biologically pure culture of the microorganism S. vellosus…capable of producing the antibiotic lincomycin upon fermentation…” was patent-eligible subject matter because the hand of man had isolated it from the jungle of nature and found that a biologically pure culture of the microorganism had a practical utility. Would these characteristics be sufficient to render a biologically pure culture of a microorganism patent-eligible today? The PTO apparently does not think so, and the Fed. Cir. has not addressed this question head-on.

Back to denvaric acid. Claim 2, the administration patch comprising a reservoir of the acid was found to be patentable. Although the acid itself is not changed by containment in the device – and so the claim recites an exception—the patch applies the acid in a meaningful way that “integrates this product of nature exception into a practical application”, citing the 1923 decision, Eibel Process.

Claims 3 and 4 are both patent-eligible because the “intermediate-acting denvaric acid” and the protamine/acid mixture both exhibit markedly changed bioactivities from pure denvaric acid. I still have trouble with the PTO’s analytic process that says, in effect, if a mixture of natural products does not occur in nature, examiners should compare the properties of the mixture to the properties of its components. If it is a simple mixture, as in Funk Bros, it is patent ineligible. However, in this case, we have been informed that the protamine imparts intermediate glycemic control properties to the denvaric acid. Because the mixture has a different effect, it is not a nature-based product and the inquiry stops with step 2B. But why not distinguish Funk Bros., or better yet, start ignoring it? Many commentators have noted that it is a decision based on novelty or patentability of a simple combination, not on patent eligibility.

There is much, much more content in the Guidelines and Examples that I simply do not have the time to explicate, or at least, summarize. I am sure that other commentators will do it for you, but I think this summary gets to the heart of the life science examples. Any and all comments are welcome.