Advances in molecular diagnostics and genetic mapping are ushering in the era of personalized medicine. Although medicine has always considered each patient individually, personalized medicine enables even more-precise and individually tailored treatment or preventive care decisions based on the patient’s genetic or molecular makeup. The ability to correlate patients’ disease or treatment with their unique genomic or molecular biomarkers allows physicians to go beyond the one-size-fits-all paradigm that may be ineffective or have undesirable side effects. Many experts consider personalized medicine as part of an overall transformation to a more cost-effective healthcare system, and several federal agencies, including FDA, have already embarked on their own personalized medicine agendas.¹

Of course, more innovations will be needed before personalized medicine can achieve widespread adoption in the healthcare system. But stakeholders in these innovations may ask what kind of intellectual property protections are available for personalized medicine. This article addresses the question of whether innovations in personalized medicine meet the basic threshold requirement for patent eligibility—that is, whether such innovations can even be considered for patent protection.

The problem can be illustrated using an example in which an oncologist is treating a breast cancer patient. The ERBB2 gene (also known as the HER2 gene) is known to be a marker for the aggressiveness of a breast tumor. Now let’s consider a hypothetical discovery that a treatment X is more effective if the patient’s ERBB2 gene contains a single nucleotide polymorphism (SNP) at sequence position 101. If the inventors sought a patent for their discovery, a patent claim might look like the claim presented in the sidebar “Hypothetical Patent Claim 3."²

The method of claim 3 is essentially the making of a treatment decision based on the genetic makeup of the patient. The method determines whether treatment X would be effective in treating the patient based on whether the patient has a SNP at position 101 of her ERBB2 gene. Patent claim 3 could be implemented by a physician viewing a laboratory report and then making a treatment decision, based on the presence of the SNP in the ERBB2 gene, about whether or not to use treatment X to treat the breast cancer patient. In other words, the diagnostic algorithm can be implemented purely through mental steps performed by the physician.

The question remains: is this algorithm-based approach to making a treatment decision eligible for patent protection? First, it may be useful to clarify that not all types of inventions are eligible for patent protection. The U.S. patent statute defines four categories of inventions that are eligible for patent protection, as follows:³

?Processes.
?Machines.
?Manufactures.
?Compositions of matter.

Although the statute appears to define a broad scope of patent-eligible subject matter for just about “anything under the sun that is made by man,” the federal courts have determined that there are certain limits.⁴ In particular, the patent laws prohibit the patenting of abstract ideas, mathematical formulas, principles of nature, natural phenomena, and mental processes (i.e., these are not patent-eligible subject matter).

From the beginning, the patent laws have never been entirely friendly to method inventions that solely involve an algorithm because they were considered abstract ideas, which are not eligible for patenting. But for a period of 10–15 years beginning in the early 1990s, the federal courts began to view such types of inventions more favorably. During this period, the general test for patent eligibility was whether the process “produced a useful, concrete, and tangible result.”⁵

This relatively loose standard for patent eligibility ushered in a proliferation of business method patents, so-called because they typically involve methods of conducting business transactions (e.g., algorithms for financial or insurance analysis, or performing Internet commerce). Under this standard, the U.S. Patent and Trademark Office (USPTO) would have considered the method in hypothetical patent claim 3 to be patent eligible because it results in a medical treatment decision, which would be considered a “useful, concrete, and tangible result.” In fact, the USPTO has granted many such types of diagnostic method patents.⁶

Bilski And Its Aftermath

With this proliferation of business method patents, however, came a backlash. Many critics argued that the patent system was impeding instead of encouraging innovation. These critics insisted that the threshold for patent eligibility should be raised, and the federal courts responded.

In 2008, the warm environment for algorithm-based inventions suddenly grew cold with the In re Bilski decision by the Federal Circuit court, which effectively negated 10 years of legal standards in the body of law governing patent eligibility.⁶ (Note: The Federal Circuit court is often referred to as the patent court for its special role in making judicial decisions related to patent law.) The Bilski case involved a method of hedging against particular investment risks in commodities trading (in what patent practitioners would consider a typical business method patent). The method was not restricted to implementation on a computer or any other sort of machine, meaning that it could be performed entirely by a person’s mental reasoning. In Bilski, the court set forth a two-part machine-or-transformation test for determining whether a process or method invention is patent eligible. The test requires that the method either be tied to a particular machine or apparatus or transform a particular article into a different state or thing. The hedging method in Bilski satisfied neither prong of this test, and thus did not qualify as patent-eligible subject matter.

Although the Bilski decision focused on business method patents, because it defines the concept of transformation in a physical sense, it affects other types of processes that primarily involve the gathering of data and interpretation of those data by human intervention. In particular, it affects patent practice in the bioinformatics fields, including personalized medicine. If a physician makes a diagnostic decision based on analyses of laboratory data, the question is whether any physical transformation has occurred.

Following the Bilski decision, the biotechnology, chemical, and pharmaceuticals technology groups at the USPTO held a customer partnership meeting on December 3, 2008. At this meeting, the USPTO offered its views on the patent eligibility of personalized medicine in a presentation titled, “A Look at Personalized Medicine.” Hypothetical patent claim 3 was shown in this presentation, and the USPTO announced that it would not qualify as patent-eligible subject matter under the Bilski decision because it is neither tied to a machine nor performs a transformation. Note that all the steps of the claim can be performed mentally by a physician.

For inventions that can be performed mentally or with pencil and paper, how can a patent claim be written to conform to the requirements for patent eligibility? In regard to this question, the USPTO announced that something like patent claim 4 would meet the patent eligibility requirements under the Bilski test (see the sidebar, “Hypothetical Patent Claim 4”).
Note that claim 4 is for a “method of treatment” instead of a “method of determination,” as in claim 3. Note also that this method is performed by a series of physical steps, instead of mental activities—namely, obtaining a nucleic acid sample, then subjecting the sample to PCR (polymerase chain reaction) analysis, and then treating the patient.

But although patent claim 4 may be patent eligible, it suffers from another potential problem. It may require multiple actors to perform the process, which can raise difficulties when the patent is enforced against an alleged infringer. Claim 4 can be implemented by one person obtaining the sample (e.g., a medical technician at a local collection facility), by another person performing the PCR analysis (e.g., a testing laboratory), and by another person performing medical treatment (e.g., a physician). In general, patent infringement requires that a single person or single entity perform all the steps of the method. In this example, if the medical technician, the lab technician, and the physician are not part of a single entity, there may be difficulty in enforcing this patent. (This issue, as well as the implications of the medical practitioner exemption from infringement liability under 35 USC 287(c), are outside the scope of this article and are not fully explored here.)

The Prometheus Case

Following the USPTO policy announcement, the Federal Circuit court offered its own post-Bilski view on personalized medicine. In the Prometheus Laboratories v. Mayo Collaborative Services case decided in summer 2009, the Federal Circuit court applied the Bilski test to a patent relating to a method for optimizing the treatment of inflammatory bowel disease by administering 6-mercaptopurine to a patient, and then determining the level of various drug metabolites as a guide to further treatment.⁷ Specifically, claim 1 of the Prometheus patent can be seen in the sidebar “Prometheus Claim 1."

Notably, the Prometheus case attracted numerous amicus brief filings (i.e., filings by noninvolved parties who volunteer their views on the case because the outcome could affect their own interests), including ones submitted by Novartis, Myriad Genetics, and the Biotechnology Industry Organization. Submission of the amicus briefs highlighted the importance of this case to the molecular diagnostics industry. The amicus brief filed by Myriad Genetics argued that patents on these types of diagnostic method inventions are critical for ensuring innovation in diagnostics and personalized medicine. Other amicus briefs argued that while Bilski’s machine-or-transformation test may be suitable for business method inventions, it is not well suited for biotechnology inventions.

These arguments appear to have been heard because the court upheld the validity of the Prometheus patent. The Federal Circuit court held that when a drug is administered to a patient, “the human body necessarily undergoes a transformation.” Thus, according to the holding in Prometheus, a claim containing a method step that involves treatment of human body tissue meets the patent-eligibility requirement set forth in Bilski.

Although the Prometheus decision is good news for medical diagnostics, the law on patent-eligible subject matter is still in a state of flux. Adding to this uncertainty, the Bilski decision is now being reviewed by the U.S. Supreme Court. The Court’s final ruling on this debate is expected in spring 2010. Amidst such uncertainty, it is clear that federal courts and the USPTO will be holding a more restrictive view of patent-eligible subject matter.

Patent Strategies

What are some strategies for patent protection of personalized medicine in this uncertain environment? One solution, as suggested by both the USPTO and the Federal Circuit, is to cast the invention as a method of treatment, rather than a method of diagnosis. This may be accomplished by including the step of administering a treatment to a patient. Another idea is to replace the data collection step with a step involving the collection of a blood or tissue sample from the patient. But although claiming treatment or sample collection steps may solve the problem of patent eligibility, it could introduce problems with enforcement if multiple actors are involved, especially if an outside laboratory performs the testing.

Activities relating to the analysis of the sample may also be added to satisfy the requirement of a physical transformation step. For example, the claim can include a biochemical reaction of the sample or the analysis of the sample can be tied to a specific diagnostic machine. Also, the diagnostic method can be tied to the use of a computer that performs the diagnostic algorithm.

Conclusion

Companies involved in molecular diagnostics should closely monitor judicial activity on the issue of patent eligibility and determine whether it affects their existing patent portfolio. It should be noted that the Bilski decision applies only to inventions that are claimed as processes or methods. Inventions that are claimed as diagnostic kits, diagnostic devices, diagnostic reagents, or biomolecular or chemical techniques are generally not directly affected by the Bilski decision.

References

1.M Rugnetta and W Kramer, “Paving the Way for Personalized Medicine,” Science Progress (September 2009).
2.K Bragdon, “A Look at Personalized Medicine,” presented at the USPTO customer partnership meeting on December 3, 2008.
3.35 USC 101.
4.Diamond v. Chakrabarty, 447 U.S. 303 (1980).
5.In re Bilski, 545 F.3d 943 (Fed. Cir. 2008).
6.For example, U.S. Patent No. 4,968,603 and No. 5,674,680.
7.Prometheus Laboratories v. Mayo Collaborative Services, No. 2008-1403 (Fed. Cir., Sept. 16, 2009).