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Getting the Prescription Right for Patenting Personalized Medicine Innovations

May 4, 2011
Pauline Farmer-Koppenol and Michael J. Shuster Ph.D.

As evolving DNA sequencing technologies drive down costs, we can soon imagine a world that includes a patient’s complete genomic sequence as part of an electronic medical record.

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“Personalized medicine” refers to the use of patient-specific information to better inform medical care. Even now, certain DNA sequence information and measures of various “biomarker” levels are used to guide diagnostic or treatment decisions. For example, the life-saving drug Herceptin® can be used as a powerful weapon in the fight against breast cancer. However, its benefits are limited to treating tumors that have a specific genetic anomaly. A simple test detects this anomaly and determines whether Herceptin® therapy will benefit the patient.

Another current example of personalized medicine comes from the cardiovascular field. At the end of 2010, Palo Alto-based CardioDx, a pioneer in the field of cardiovascular genomic diagnostics, announced that Corus™ CAD, the company’s blood-based gene expression test, was honored as one of Time magazine’s “Top Ten Medical Breakthroughs of 2010.” Corus™ CAD is the first and only clinically-validated blood-based test to help clinicians confidently identify which of their stable symptomatic patients are likely to need further assessment for obstructive coronary artery disease.

The list goes on to include tests that determine disease progression in rheumatoid arthritis (Crescendo Bioscience), risk of developing diabetes (Tethys Biosciences), risk of transplant rejection (XDx – Expression Diagnostics), tests to assess breast and ovarian cancer risk (Myriad Genetics), and those used to guide treatment decisions for breast and colon cancer patients (Genomic Health).

As evolving DNA sequencing technologies drive down costs, we can soon imagine a world that includes a patient’s complete genomic sequence as part of an electronic medical record. Incorporating individualized genomic information into medical practice moves us into what Lee Hood refers to as “P4” paradigm, i.e., predictive, preventive, personalized, and participatory medicine. However, much work remains to translate this promise into a new reality. Development, validation, approval, and reimbursement of new diagnostic tests that translate this information into useful indicators of an individual’s disease risk, or an optimal treatment approach, requires private sector investment in nascent personalized medicine companies.

Such investments are protected by our patent system. Patents provide companies with time-limited exclusive rights to exploit their inventions and recoup a reasonable return on the considerable investment needed to develop these tests and bring them to market.

Patent protection for personalized medicine inventions is currently in a state of flux. The majority of disputes are over the eligibility of personalized medicine inventions for patent protection under 35 U.S.C. § 101. In one recent case, Prometheus Labs., Inc. v. Mayo Collaborative Servs., 628 F. 3d 1347 (Fed. Cir. 2010), petition for cert. filed, (U.S. Mar. 17, 2011) (No. 10-1150), the claims at issue were directed to methods of optimizing therapy for specific drugs (6-Mercaptopurine and azathioprine) by determining whether specific metabolite levels were above or below a threshold. Levels exceeding the threshold indicate that dosing should be adjusted downward, and vice versa. All claims recite determining the level of metabolite. Some claims also recite administering the drug prior to the determining step.

The case was before the U.S. Court of Appeals for the Federal Circuit the first time in 2009. Applying the machine or transformation test that the court had articulated in its decision in In re Bilski, 545 F. 3d 943 (Fed. Cir. 2008), the court decided that both administering a drug to a patient and determining metabolite levels satisfied the transformation prong of the machine or transformation test. The court reasoned that the body is transformed by administering the drug, and that the sample is transformed by the processes used to determine metabolite levels. Mayo Collaborative appealed this decision to the U.S. Supreme Court, which remanded the case back to the Federal Circuit in light of Bilski v. Kappos, 130 S. Ct. 3218 (which held that the machine or transformation test provides an “investigative tool” to patentability, but is not a necessary condition for patentability).

On remand, the Federal Circuit affirmed its previous Prometheus decision, confirming that the claims at issue are patent eligible. For those claims including a drug administering step, the court stated, “[t]he transformation is of the human body and of its components following the administration of a specific class of drugs and the various chemical and physical changes of the drugs’ metabolites that enable their concentrations to be determined. We thus have no need to separately determine whether the claims also satisfy the machine prong of the test.” As for claims that did not include “administering” the Court reiterated its position that the metabolite determining step “necessarily involves a transformation.” Quoting a Prometheus expert, the court noted that, “at the end of the process, the human blood sample is no longer human blood; human tissue is no longer human tissue.”

Mayo argued that the claims at issue were assay-and-correlate-style LabCorp claims (based on simple correlations between two substances inherently resulting from underlying physiology) and cast the claims as an improper attempt to patent a natural phenomena (i.e., the underlying physiology). It is important to note that the claims at issue in LabCorp were not analyzed for patent eligibility under 35 USC § 101. LabCorp of Am. Holdings v. Metabolite Labs, Inc., 584 U.S. 124 (2006). In an opinion dissenting from the Supreme Court’s dismissal of certiorari for LabCorp Justice Breyer suggested that he found such “assay-and-correlate” claims to be an impermissible attempt to patent a natural phenomena.

The Court addressed arguments that drug transformation into a metabolite is merely a reflection of a natural phenomenon. “As Prometheus points out, quite literally every transformation of physical matter can be described as occurring according to natural processes and natural law. Transformations operate by natural principles. The transformation here, however, is the result of the physical administration of a drug to a subject to transform—i.e., treat—the subject, which is itself not a natural process.”

The court also addressed the issue of pre-emption. Mayo had argued that Prometheus’s claims “preempt all practical use of naturally occurring correlations between metabolite levels and drug efficacy and any machine or transformation present in the claims is merely insignificant post solution activity.” The court answered that “Prometheus’s claims are drawn not to a law of nature, but to a particular application of naturally occurring correlations, and accordingly do not preempt all uses of the recited correlations between metabolite levels and drug efficacy or toxicity.” The court pointed out that the claims include limitations drawn to specific disease, drugs and metabolites. These are key facts supporting the patent-eligibility of the claims under a pre-emption analysis.

We had previously reported that the Supreme Court’s Bilski decision suggested that advanced medical diagnostics, such as those that use information derived from multiple genetic variations or biomarker expression levels, fall within the scope of patentable subject matter. The Federal Circuit’s remand decision in Prometheus provides additional support for the patentability of diagnostic inventions, including those whose claims do not require administering of a drug prior to performing a diagnostic test.

Further clarity will hopefully come in the court’s decision in Classen Immunotherapies, Inc. v. Biogen IDEC. In a non-precedential opinion of 69 words issued before the Supreme Court’s Bilski decision, the Federal Circuit found the claims at issue in Classen not to be patent eligible. 304 Fed. Appx. 866 (Fed. Cir. 2008). The Supreme Court then remanded the case back to the Federal Circuit; a decision is expected this year. 130 S. Ct. 3541 (2010).

Classen’s claim 1 is to a method of determining whether an immunization schedule affects the incidence or severity of chronic-immune-mediated disorders and is similar to the claim at issue in Prometheus in that it recites administering an immunogen and optionally determining a level of a marker of a disorder. It is however not limited to a particular immunogen, class of immunogens, disorder, class of disorders or marker or class of markers. Should the Federal Circuit find this claim patent-eligible in its remand decision, it would provide even greater scope for patentability of diagnostic claims. However, we predict that the court will draw a line between the Prometheus claims, which recited a particular disorder, particular drugs and particular metabolites, and claims like Classen’s claim, which are not so limited. Thus, we recommend keeping an eye on how pre-emption analysis develops in the 101 case law, and when drafting claims, to include claims likely to survive such analysis because they meaningfully restrict scope and so avoid §101’s “natural phenomenon” exception.

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