In Ex Parte Timothy, the USPTO Patent Trial and Appeal Board (PTAB) affirmed the Examiner’s rejection of personalized medicine treatment claims. This decision highlights the PTAB’s willingness to invalidate claims that it finds similar to the claims at issue in Mayo. It also underscores the need for Congressional action to incentivize and protect investments in this important frontier of health care.

The Personalized Medicine Treatment Claims

The decision was rendered in U.S. patent application 13/269,365, assigned to SureGene LLC. According to the background section of the application, in the treatment of psychotic disorders, “there are individual differences in response to specific drugs based on differences in drug pharmacology and metabolism, combined with genetic differences between patients.” Also according to the application, “[t]here are currently no proven ways to identify which antipsychotic drug is optimal for a given patient. Thus, patients switch from one drug to another when response is not considered to be adequate or side effects are intolerable.” Indeed, “[o]n average, each patient may change medications three times for finding one that works.”

The application describes the invention as being “in part based on the finding that a genetic signature, which the inventors refer to as the Olanzapine Poor Response Predictor (OPRP), is a biomarker that can be used for selecting a more appropriate antipsychotic treatment plan for that particular subject. For example, the inventors have discovered that patients that are OPRP negative respond better than patients that are OPRP positive when treated with olanzapine, clozapine, or quetiapine.”

Claim 1 was identified as representative:

1. A method for treating a human subject having or suspected of having a psychotic disorder, comprising:
a) selecting a subject having or suspected of having a psychotic disorder and who has been determined to
have the OPRP genetic signature, wherein the OPRP genetic signature is defined as a genotype comprising a homozygous genotype for the T allele at rs11960832 and either a homozygous or heterozygous genotype for the T allele at rs7975477; and
b) treating the subject that was determined to have the OPRP signature with an antipsychotic treatment other than clozapine or quetiapine.

The PTAB Decision

The PTAB summarized the § 101 rejection on appeal:

The Examiner has rejected claims 1-10 as being directed to patent-ineligible subject matter. The Examiner finds that, under the standard set out in Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66 (2012), “the claims inform a relevant audience about certain laws of nature. The additional steps consist of well-understood, routine, conventional activity already engaged in by the scientific community. The additional steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” (Final Action 5.)

The Examiner also had found:

• the correlation between the OPRP genetic signature and response to clozapine or quetiapine treatment is a “law of nature” under Mayo

• the “selecting” is not sufficient to transform the claim into eligible subject matter

• the “treatment” step did not distinguish the claims from Mayo, because the claims at issue in that case also were directed to a method of treatment.

The PTAB agreed, and set forth the claims from Mayo in its decision:

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 levels of 6–thioguanine below or above certain thresholds indicate a need to increase or decrease, respectively, the amount of drug being administered.

The PTAB drew several analogies to the Mayo decision, including:

The Court [in Mayo] concluded that “[a]nyone who wants to make use of these laws must first administer a thiopurine drug and measure the resulting metabolite concentrations, and so the combination amounts to nothing significantly more than an instruction to doctors to apply the applicable laws when treating their patients.” …. Similarly here, anyone who wants to make use of the natural law–the relationship between the OPRP genetic signature and the lack of efficacy of clozapine or quetiapine –must first determine whether a given patient has the OPRP genetic signature before determining which antipsychotic medication to treat them with. Thus, claim 1 amounts to nothing significantly more than an instruction to doctors to apply the applicable law when treating their patients.

The PTAB rejected the argument that the claim should be eligible as a new use of a known drug, because “the treatment of schizophrenic patients with antipsychotic drugs other than clozapine or quetiapine does not represent a new use for the known antipsychotic drugs.” Thus, the PTAB did not give any weight to the patient selection steps when determining that the claim related to a known use of a known drug.

The PTAB also rejected the argument that the claim should be eligible by analogy to the USPTO’s amazonic acid example, asserting that “the cited exemplary claims address analysis of a different class of inventions that have been held to be patent-ineligible,” i.e., natural products that are analyzed under Myriad. The PTAB emphasized, as it has in other decisions, that it is not bound by the USPTO’s Subject Matter Eligibility Guidelines.

Inconsistency Won’t Incentivize Investment

Subject matter eligibility was a hot topic at the IPO Annual Meeting last week. Even though panelists didn’t agree on the best way to address the recent changes in this area of U.S. patent law, everyone agreed that predictability–the ability to know what is and what is not patentable–is essential to making sound business and investment decisions. In that context, it is striking that the PTAB relied on a 2012 Supreme Court decision (Mayo), even though SureGene had obtained several personalized medicine patents since that case was decided–including patents granted as recently as 2015.

The PTAB’s unwillingness to adhere to the USPTO’s Subject Matter Eligibility Guidelines also is disturbing, and makes the patent application process even more inconsistent and unpredictable. While the PTAB had grounds for distinguishing the “amazonic acid” claims, it did not address–or even expressly acknowledge–the diagnosing and treating claims of the “julitis” example, which are said to be eligible in an analysis that considers the contribution of the claimed “combination of steps,” gives weight to the fact that the combination “is not routine and conventional,” and finds “significantly more” in “ensur[ing] that patients who have julitis will be accurately diagnosed (due to the detection of JUL-1 in their plasma) and properly treated.” An Examiner following these Guidelines could grant claims that an Examiner not following the guidelines would not, and the PTAB might uphold the Examiner who did not follow the guidelines!

Also a hot topic at the IPO Annual Meeting was possible legislative changes to § 101. While not all stakeholders agreed that Congressional action is needed to address issues facing computer and business method patents, most agreed that diagnostic methods and personalized medicine should be brought back into the realm of eligible subject matter, such as by legislation that would at least abrogate Mayo, if not Myriad.

On this point, it is important to keep in mind that SureGene’s patent application at issue here was filed before the Supreme Court decision in Mayo. Thus, SureGene invested in this technology against a landscape where it would be patentable. How can we expect continued innovation in these fields without patent protection?