NOA v. DOA: Increasing Medical Diagnostic Patentability After Mayo.

• Author: McKenzie, Karen

INTRODUCTION I. PATENTABILITY OF MEDICAL DIAGNOSTICS A. Dissecting the Prometheus Patent B. Mayo and its progeny: Alice Corp, Myriad and Sequenom C. PTAB Cases & USPTO Guidance II. RESOLUTION CONCLUSION APPENDIX Introduction

The medical diagnostics market is expected to reach 65 billion by 2018. (1) In March 2012, in Mayo Collaborative Services v. Prometheus Labs, Inc., ("Mayo") the U.S. Supreme Court held that the Mayo Clinic (the "Clinic") had not infringed on Prometheus Labs' ("Prometheus") diagnostic patent because the Prometheus patent involved ineligible subject matter, and was therefore invalid. (2) Section 101 of the Patent Act defines eligible subject matter as "any new and useful process, machine, manufacture, or composition of matter" as patentable subject matter. (3) Courts have held that Section 101 contains an implicit exception, making laws of nature, natural phenomena, and abstract ideas ineligible for patent protection. (4) Traditionally, applications to a structure or process have satisfied this exception. (5)

However, since the Court's unanimous decision in Mayo, the percentage of medical diagnostic patents allowed (6) by the U.S. Patent & Trademark Office (the "USPTO") has dropped to less than thirty-five percent, as compared to eighty-five percent before Mayo. (7) Mayo and its progeny (8) arguably had a significant impact on the multi-billion-dollar medical diagnostic industry--an industry focused on the laws of nature that occur within the human body. After Mayo, medical diagnostics developers have encountered less certainty for both issuance and in mounting a vigorous defense of infringement.

Although the topic of patentability has been avidly discussed in legal literature critiquing the Court's Mayo rationale, this article will analyze possible solutions to increase patentability, and the defense of medical diagnostic patents. Specifically, this article will examine: (1) how the Prometheus patent could have been altered during patent prosecution; (2) how these changes are affected by a challenge of invalidity elucidated through Mayo and its progeny; and (3) whether the Patent Trial and Appeal Board (the "PTAB") or subsequent Federal Circuit decisions have clarified the patentability of medical diagnostic patents. Finally, this article will draw conclusions regarding strategies to increase patentability in medical diagnostic patents and reduce the likelihood that the patent will be pronounced "Dead on Arrival" (DOA9) in district court.

1. Patentability of Medical Diagnostics

   1. Dissecting the Prometheus Patent

      The Prometheus patent assessed the proper therapeutic blood level of drugs used to treat Crohn's disease and ulcerative colitis. (10) Essentially, the patent applied principles of pharmacokinetics to customize the dosage for each individual patient, and therefore minimize toxicity while optimizing the therapeutic value of the medication. (11) The Clinic licensed the patented steps for determining these individualized dosages. (12) Eventually, the Clinic developed and used its own process; and Prometheus subsequently sued for infringement. (13) A U.S. District Court determined that the Clinic infringed on Prometheus's patents, but that Prometheus's patents were invalid. The U.S. Court of Appeals for the Federal Circuit overturned part of that decision, holding that Prometheus' diagnostic test was valid. (14) The Clinic subsequently appealed. (15)

      The U.S. Supreme Court held that the processes in the diagnostic test were ineligible subject matter because the processes pertained to laws of nature under 35 U.S.C. [section] 101 of the Patent Act. (16) Although "an application of a law of nature ... to a known structure or process may [deserve] patent protection," a law of nature cannot be transformed "into patent eligible [matter] ... simply [by] stat[ing] the law [and] adding the words, 'apply it.'" (17) The Court therefore found that the "steps" Prometheus added to the process were not novel; instead they were merely instructions regarding a law of nature. (18) Thus, Mayo altered the landscape of the machine-transformation test, which up to that point, had been applied to other processes. (19) Medical diagnostics largely revolved around laws of nature played out within the human body and so long as a novel application was applied, the USPTO, the Federal Circuit, and Supreme Court did not cry foul. However, after Mayo, previously accepted additional requirements for process patentability to survive a law of nature invalidation would no longer be enough. In fact, simply adding the language "apply it" would not be enough. (20)

      In light of this, the U.S. Supreme Court remanded Mayo to the Federal Circuit to determine whether transforming a law of nature was an adequate transformation to make Prometheus' diagnostic test patentable. (21) On remand, the Federal Circuit reasoned that it "is virtually self-evident that a process for a chemical or physical transformation of physical objects or substances is a patent-eligible subject matter[.]" (22) However, the Supreme Court found that the administering and determining steps of the Prometheus patent were not transformative, but merely "insignificant extra-solution activity[.]" (23) Additionally, the machine-or-transformation test must transform an ineligible material into eligible material. (24)

      The Court addressed this complex transformation challenge, inherent within medical diagnostics, by discussing the risk of making overly broad claims and whether a claim has presented a "substantial practical application," (25) reinforcing that "laws of nature, natural phenomenon, and abstract ideas" cannot be granted patent protection. (26) Historically, until the mid-2000's, 35 U.S.C. [section] 101 was interpreted quite broadly to include many types of subject matter; however, laws of nature were never patentable except for diagnostic methods claims that were routinely granted by the USPTO. Challenges to their status as patentable subject matter were not typically raised during litigation.

      Mayo marks a distinct departure from this historical treatment of diagnostics. Reciting a process "is no more than a[n] ... instruction to [read some numbers in light of medical knowledge]." (27) Upon review of Prometheus' '632 patent claims 1-54, the following claims construction language is repeated in claims 1,7, 15, 25, 37 and 46:

      (1) A method of optimizing therapeutic efficacy for treatment of a ... disorder:

      (a) administering a drug ... to a subject having said ... disorder; and (b) determining the level of [drug] in said subject having ... disorder, wherein the level of [drug] less than about 230 pmol per 8 x [10.sup.8] red blood cells indicates a need to increase the amount ... drug subsequently administered to said subject and wherein the level of 6-thioguanine greater than about 400 pmol per 8 x [10.sup.8] red blood cells indicates a need to decrease ... drug subsequently administered.

      (7) A method of reducing toxicity associated with treatment of a ... disorder, comprising:

      (a) administering a drug providing 6-thioguanine to a subject having said ... disorder;

      (b) determining the [amount of the drug] ... in said subject having ... disorder; and

      (c) determining the level of 6-methyl-mercaptopurine in said subject having said ... disorder, wherein the level of 6-thioguanine greater than about 400 pmol per 8x[10.sup.8] red blood cells or the level of 6-methylmercaptopurine greater than about 7000 pmol per 8x[10.sup.8] red blood cells indicates a need to decrease the amount of ... drug subsequently administered. (28)

      The claims construction language of "administering, determining, and administering," does not describe a non-conventional or novel activity. Indeed, this activity describes what is commonly known as pharmacokinetics and pharmacodynamics. (29) Arguably, what is missing from the '623 patent claims is some form of unique step that may have enabled a more effective adjustment of the blood levels of the drug in question. This could have been supported by a unique mathematical algorithm, a more discrete lab test with a higher degree of sensitivity and specificity than other tests on the market, or a process that was more advanced in regard to the accuracy of predicting toxicity and therapeutic levels in a specific population. Such a process of determining toxicity with a higher degree of sensitivity, could in turn allow, for example, less frequent blood draws, and more accurate determinations. However, this type of disclosure was absent in the '632 patent and was historically not required by the USPTO to issue a patent or the courts in the defense of diagnostic patents.

      In contrast, Classen v. Biogen Idee, decided before Mayo but still relevant, claimed a method directed to immunizing a patient based on detection of markers in a screening step. (30) Although the screening step was based on a natural law, the immunization step was a non-conventional specific application of the screening principle, (31) and this claim was held as patentable. (32)

      A similar diagnostic test that was based on natural law--yet, held as patentable--was the subject of litigation in Ameritox Ltd. v. Millennium Health, LLC. (33) The Ameritox invention was specifically directed "to quantify[] the metabolite concentration by adjusting the concentration for the patient's hydration status, and then statistically comparing the adjusted concentration to a set of known normative data." (34) In this way, the invention provided a method to improve medication monitoring and identify aberrant drug use. More importantly, the Ameritox '680 patent identified statistical analysis and normative data that increased the sensitivity and specificity of the test rendering it an inventive concept. (35)

   2. Mayo and its progeny: Alice Corp, Myriad and Sequenom

      Ameritox provides an excellent discussion of how Alice Corporation v. CLS Bank International outlines the framework for analyzing...