Inventors of methods of medical testing have had a rough time since the Supreme Court decided Mayo Collaborative Services v. Prometheus Labs. Inc. In the Mayo case, the Court considered whether a method of determining whether a patient is receiving the proper dosage of thioguanine drugs is eligible for patenting, when the method involved measuring the concentration of a specific metabolite of thioguanine in the patient’s blood. The inventor had determined the safe range of dosages was not based not on the dosage itself (which varied a great deal from person to person), but depended on the concentration of the metabolite. The Court concluded that the patent merely claimed a relationship between metabolite concentration, safety, and efficacy of the drug, which without more is not an invention.

Since Mayo was decided, courts have invalidated numerous medical testing patents as subject matter that is not eligible for patenting (See, e.g., Cleveland Clinic Foundation v. True Health Diagnostics, LLCGenetic Tech. Ltd. v. Merial LLC, Ariosa Diagnostics, Inc. v. Sequenom, Inc., SmartGene, Inc. v Advanced Biological Labs.,  and PerkinElmer Inc. v Intema Ltd.).

A Rare Win for a Medical Testing Patent in <i>Exergen Corporation V. Kaz USA, Inc.</i>This makes the recent decision by a panel of the U.S. Court of Appeals for the Federal Circuit in Exergen Corp. v. Kas USA, Inc. something of a unicorn. Exergen patented a forehead thermometer that functions by measuring the radiative output of the skin at least three times per second, identifying a peak temperature that indicates that the thermometer has passed over an artery, and executing an algorithm based on the peak temperature and the ambient air temperature to calculate the patient’s core body temperature. Some of the asserted patent claims included the limitation that the artery is the temporal artery (located in the side of the forehead). The Exergen thermometer has the advantage over prior art thermometers of measuring a patient’s core temperature noninvasively, a benefit every parent can appreciate. Several companies, including Kaz, offered similar forehead thermometers, and Exergen filed several infringement suits in the U.S. District Court for the District of Massachusetts, which were consolidated only for claim construction purposes. Among other defenses, Kaz alleged that all of Exergen’s asserted patent claims were invalid as non-eligible subject matter for patenting under the Mayo decision.

The Trial Court Decision

At trial the judge ruled from the bench that the asserted claims were eligible subject matter as a matter of law. The jury found that Kaz infringed the patents and awarded damages. On appeal Kaz argued that the trial court had impermissibly decided the question of patent eligibility without sending the relevant factual questions to the jury, and, in the alternative, that Exergen’s claims were not patent eligible as a matter of law.

The Appellate Decision

Among the claims at issue were both method claims and apparatus claims. Claim 24 of the ‘685 was considered by the appellate court as typical of the apparatus claims, and reads as follows:

A body temperature detector comprising:

a radiation detector; and

electronics that measure radiation from at least three readings per second of the radiation detector as a target skin surface over an artery is viewed, the artery having a relatively constant blood flow, and that process the measured radiation to provide a body temperature approximation, distinct from skin surface temperature, based on detected radiation.

Note that the electronics are defined mainly by their function. Claim 14 of the ‘938 was considered by the appellate court as typical of the method claims, and reads as follows:

  1. A method of detecting human body temperature comprising

making at least three radiation readings per second while moving a radiation detector to scan across a region of skin over an artery to electronically determine a body temperature approximation, distinct from skin surface temperature.

The court applied the general test in Alice for patent eligibility (readers of this blog can review the Alice test here). The court found that the claims fell under the categories of subject matter Congress intended should be patented, as expressed in 35 U.S.C. § 101, as “machines” and “processes.” The court went on to conclude the claims were “directed to” one of the judge-made exceptions to the statutory categories, specifically the “law of nature” that physiologic core temperature is a function of skin temperature above an artery and ambient temperature. Based on these two conclusions, a claim would not be eligible for patenting unless as a whole it encompasses “substantially more” than natural law itself.

Kaz argued that the claims were not substantially more than the simple recognition of the relationship between skin temperature above an artery, ambient temperature, and core temperature. In Kaz’s view, the remaining parts of the claims were “conventional, well understood” elements. In support of this argument, Kaz cited the undisputed fact that the use of infrared radiation measurements of the skin to detect internal injuries was known before Exergen’s invention, and such measurements were made at a rate exceeding three readings per second.

The appellate court disagreed with Kaz’s argument and affirmed the district court’s finding that the claims were directed to substantially more than the natural law. Regarding the older method of detecting internal injury, the court pointed out that “Something is not well-understood, routine, and conventional merely because it is disclosed in a prior art reference… This case is not like either Mayo or Ariosa, where well-known, existing methods were used to determine the existence of a natural phenomenon.” In other words, the inventors in Mayo and Ariosa identified the relationship between an analyte and a condition, and claimed measuring the analyte by only well-understood, routine, and conventional methods (in Mayo the broadest claims were not specific to the measurement methods at all). Exergen’s claims included an unconventional method of determining core body temperature, which was novel independent of the recognition of the specific relationship between the temperature of the skin above an artery and the patient’s core body temperature. Although body radiation sensors were known, none had been configured to convert skin temperature to core temperature; although methods of measuring skin temperature with a radiation sensor were known, none had specifically measured skin temperature above and artery and converted it to core temperature.

How Does Exergen Fit with Current Case Law?

Comparing Exergen to Mayo, in Mayo the measurement of the metabolite was claimed generally, not by any specific method, conventional or otherwise. Measuring the metabolite was well-known and conventional. The claims in Mayo thus involved only a well-known and conventional step, in combination with reaching a diagnosis. Although the criteria used for the diagnosis were not previously known, others had tried to use the metabolite concentration to diagnose the same condition using different criteria. In contrast, Exergen claimed steps that had never been performed before — measuring skin temperature over an artery by radiometry, in addition to the more abstract steps of calculating core temperature.

The distinctions between this case and Ariosa are more subtle, and the two cases might seem inconsistent. The patent in Ariosa did claim steps that had never been performed before; namely, it recited amplifying paternal DNA in a maternal whole blood sample. The court focused on the fact that the paternal DNA was claimed to be measured by conventional methods (polymerase chain reaction), so that nothing substantial was added to the concept of measuring the paternal DNA itself. In Exergen, the court defined the measured property as body core temperature, and found that it was neither routine nor conventional to measure body core temperature as claimed. However, if the court had considered ultra-arterial skin temperature to be the measured property, instead of core temperature, it might have concluded that the claimed steps were conventional and well-understood ways of measuring it.

This distinction can serve as guidance going forward: Defining exactly what is being measured can be determinative of the Alice analysis of medical tests. Those seeking to patent or defend medical testing claims could benefit from defining the measured property narrowly. Alternatively, those seeking to invalidate medical testing patents should seek to define the measured property broadly as something that has been measured before in the same way. For example, does the invention measure core temperature by measuring ultra-arterial skin temperature by radiometry, or does it measure skin temperature by radiometry? The latter steps were known in the prior art, while the former were not.

Diagnostic and Personalized Medicine Claims -- Strategies for Navigating the §101 MinefieldIn Cleveland Clinic Foundation v. True Health Diagnostic LLC, the Federal Circuit (CAFC) dealt another blow to the patent eligibility of diagnostic methods and the growing field of personalized medicine.

Cleveland Clinic obtained three patents (US Patent Nos. 7,223,552, 7,459,286 and 8,349,581) directed to the use of the activity and/or levels myeloperoxidase (MPO) or a MPO oxidation products (the foregoing referred to as simply MPO in this discussion) to characterize/assess/predict a risk of cardiovascular disease in a subject. At a high level, the claims required: 1) determining a level/activity of MPO in a subject; 2) comparing this value with a control value; 3) and determining risk of disease when the MPO level/activity is increased as compared to the control. The claims in the patents also describes various forms and features of cardiovascular disease, such as when a cardiovascular event might occur.

The CAFC used the Alice two-step framework and found the claims were directed to “multistep methods for observing the law of nature that MPO correlates to cardiovascular disease” under step one and no feature of the claims, either alone or in an ordered combination, was sufficient to transform the law of nature into a patent-eligible concept under step two (citing the use of prior art techniques to detect MPO and statistical methods to determine the level of MPO and the control value). There was nothing dramatically different in the court’s Alice analysis than in previous cases.

Is a Correlation a Law of Nature?

The courts have consistently refused to provide a concrete definition of what is a natural law or an abstract idea. The courts rely heavily on determinations in prior cases to guide the inquiry. It could be argued there is no “natural law” that a subject with a high level of MPO will have an increased risk of cardiovascular disease. In some cases the correlation will not prove true, but in some cases it will. In many subjects, a high level of MPO will be asymptomatic (perhaps due to other aspects of the subject’s physiology). Likewise, many subjects with low MPO levels will have cardiovascular disease due to factors unrelated to MPO levels (for example, poor lifestyle or genetic predisposition). Furthermore, the correlation was shown to vary in certain aspects depending on the population studied and the time frame with which a cardiovascular event might occur. Given these discrepancies, is a correlation that holds true for only a portion of a population or only under certain defined conditions properly defined as a natural law?

Characterizing the Improvement over the Prior Art

Let’s take a step back and look at the claims in the context of the prior art. The claimed methods allow an improvement in the technological field or medical care. The simple blood test allows for the identification of patients that may benefit from additional care without invasive testing at a low cost using a simple procedure. The CAFC recognized the difference in the claimed methods (one of which detected MPO in the blood but was not predictive of cardiovascular disease) and the benefits of the claimed methods. Viewed in this manner, the claims are similar to those in Diamond v. Diehr, where an abstract idea was held to be patent eligible when the abstract idea was used in a process designed to solve a technological problem in conventional industry practice.

The CAFC distinguished this case from Rapid Litigation Management, Ltd. v. CellzDirect, where claims directed to a method of cryopreserving cells were eligible under §101, as we discussed in a previous post. In CellzDirect, the basis for the claimed methods was the discovery of an inherent property of liver cells to undergo multiple freeze-thaw cycles while still maintaining viability. The methods claimed in CellzDirect, such as those here, did not invent new techniques for the cryopreservation process (prior art methods and reagents were used), but rather claimed additional steps in the cryopreservation process based on the discovered natural property of liver cells to provide a new and useful laboratory technique. The method claims in this case take the presumed natural law of MPO correlation to certain types of cardiovascular disease and add additional limitations (for example, time frames for the onset of disease) or steps (for example, comparison to a control value) to produce a new and useful laboratory technique.

One possible reason for the holding in the present case may be the lack of specific information on how an “elevated” MPO level is determined, how the control value is determined, or how much above the control value the MPO level in the subject needs to be in order to be at risk for the defined conditions. The provision of such a defined decision point would have allowed arguments that the claims were directed not to the presumed natural law, but to a specific value derived by the hand of man. As such, the claims would not “start and end with the naturally occurring phenomenon” as prohibited in Ariosa.

Such a decision point could be implemented using an algorithm or “rule set” that provides cut-off values and criteria for the evaluation of the subject’s risk based on MPO levels and possible other risk factors (the specification discusses several, such as troponin-T). Such a rule set could also specify comparisons among discrete populations. While the use of such rule sets obviously limits claim scope to some extent, defining the claimed relationships with greater specificity offers additional arguments in the eligibility battle. An additional benefit is this approach potentially allows the omission of an explicit comparison step (as any comparison is accomplished by the rule set).

The use of rule sets was favorably viewed by the CAFC in McRO v. Bandai, noted in a previous post, where the court allowed a rather generic rule set to provide for §101 eligibility in a method of computer animation. The CAFC noted that the rule set in McRO “transformed a traditionally subjective process performed by human artists into a mathematically automated process executed on computers.” Claims that define the MPO correlation to a baseline value in determining an outcome should be viewed as transforming the subjective process of diagnosis into a defined process carried out by the claimed methods. While McRO is directed to the computer arts, the mantra of the CAFC is that each technological field is treated the same in terms of patent eligibility analysis.

Conclusion

While the CAFC held the claims at issue here to be invalid under §101, I do not believe the door is shut for meaningful patent claims directed to diagnostic methods and their use in personalized medicine. While the prevailing judicial view may require the recitation of additional elements with more specificity, thoughtful drafting of the specification and claims provides an opportunity for claims of the type invalidated here to withstand the scrutiny of the §101 analysis.

USPTO Issues Patent Eligibility Guidance In View Of CellzDirect and SequenomThe USPTO issued a memorandum to the examining corps entitled Recent Subject Matter Eligibility Rulings (Rapid Litigation Management v. CellzDirect and Sequenom v. Ariosa) on July 14, 2016. The Patent 213 Blog has previously reviewed each of these cases. The USPTO notes that the decisions do not change the subject matter eligibility framework and that the subject matter eligibility guidance previously issued is consistent with both CellzDirect and Sequenom. The USPTO did, however, acknowledge that the CellzDirect decision provided guidance on the proper inquiry for determining whether the claims are “directed to” a judicial exception.

In the CellzDirect decision, the Federal Circuit found the claims patentable under step one of the Alice framework (which corresponds to Step 2A in the USPTO’s analytical framework). Specifically, the court characterized the claims as being directed to “a new and useful laboratory technique for preserving hepatocytes” and determined that such processes carried out to achieve “a new and useful end is precisely the type of claim that is eligible for patenting.”

The July memorandum takes notice of several important points in the CellzDirect decision. Specifically, the USPTO quoted the portion of the CAFC’s opinion outlining the requirements under the “directed to” inquiry. In CellzDirect, the panel noted the “directed to” analysis of a process claim requires more than “merely identify[ing] a patent-ineligible concept underlying the claim” and instead requires an analysis of whether “the end result of the process, the essence of the whole, was a patent-ineligible concept.” In discussing this point, the July Memorandum notes that the claims in CellzDirect were not simply an “observation or recitation” of the ability of hepatocytes to survive multiple freeze-thaw cycles but were directed to specific process steps that manipulated the hepatocytes to “in accordance with their ability to survive multiple freeze-thaw cycles.” The July Memorandum stresses determination of the “focus” of the claims under the directed to inquiry. The claims in CellzDirect, as focused on the process for achieving the desired outcome, were not directed to the judicial exception.  The USPTO noted that a similar approach was used in the recent Enfish decision.

The “directed to” INQUIRY requires an analysis of whether the end result of the process, the essence of the whole, was a patent-ineligible concept.

Finally, the distinction made by the Federal Circuit between the claims in CellzDirect on one hand and Sequenom and Mayo on the other was noted. The claims in Mayo and Sequenom, rather than being focused on a process for achieving a desired outcome “were found to be directed to a patent-ineligible concept when they ‘amounted to nothing more than observing or identifying the ineligible concept itself.’”

Regarding Sequenom, the July Memorandum specifically notes that the U.S.S.C.’s denial of cert “does not elevate” the significance of the original decision or alter the way in which the original decision is applied.