In Greek mythology, Prometheus was a titan who played a pivotal role in the early history of mankind by stealing fire from Zeus and giving it to mortals. On March 20, the U.S. Supreme Court launched its own fireworks through the medtech industry by issuing its titanic decision regarding medical diagnostic patents in Mayo Collaborative Services v. Prometheus Laboratories Inc. The “Prometheus” decision will directly impact diagnostics, personalized medicine, and genomic patents, and has sent shockwaves through the medtech and life-sciences industries.

In a unanimous decision, the U.S. Supreme Court invalidated two patents covering the optimization of the therapeutic efficacy of a drug regimen as claiming patent-ineligible subject matter. In doing so, the Supreme Court reversed the Court of Appeals for the Federal Circuit that twice upheld the patentability of the diagnostic method patent claims. The Supreme Court’s Prometheus decision held that all claims of the two patents are invalid as directed to unpatentable “laws of nature.”

The ruling is causing uncertainty and concern in the diagnostics and personalized medicine fields, where some of the world’s largest pharmaceutical companies are trying to target treatments to the unique genetic makeup of a patient through use of diagnostic tests. Although this ruling indicates a willingness of the Supreme Court to address perceived problems in the patent system, it also introduces new standards and uncertainties. To build and maintain a strong patent portfolio, medtech companies will need to pursue patent strategies that account for this major decision.

A Summary of the Case

Prometheus Labs is the exclusive licensee of two patents covering methods for determining patient-specific dosing for thiopurine drugs to treat autoimmune diseases such as Crohn’s disease and ulcerative colitis. The invention was based on the discovery of a correlation between the safety and efficacy of a specific dosage and level of metabolites measured in the blood of a patient.

In 2004, Prometheus Labs filed a patent infringement lawsuit against the Mayo Clinic, alleging that Mayo’s diagnostic test for measuring the metabolism of the thiopurine drugs in the treatment of autoimmune diseases infringed U.S. Patent Numbers 6,355,623 and 6,680,302. In 2008, the district court granted a summary judgment of invalidity of the two patents because the claimed methods were directed to non-statutory subject matter under 35 U.S.C. §101. The Court of Appeals for the Federal Circuit reversed in 2009, and Mayo filed a petition for a writ of certiorari (a document that a losing party files with the Supreme Court asking it to review the decision of a lower court. It includes a list of the parties, a statement of the facts of the case, the legal questions presented for review, and arguments as to why the Court should grant the writ). The Supreme Court granted certiorari to review the decision, and remanded the case back to the Federal Circuit in light of the Supreme Court’s major 2010 decision regarding patentable subject matter in Bilski v. Kappos. On remand, the Federal Circuit again held on Dec. 17, 2010, that the two patents claimed patentable subject matter because both the “administering” and “determining” steps of the patent claims were transformative, satisfying the machine-or-transformation test set forth in Bilski.

The Supreme Court then granted review of the second Federal Circuit opinion and heard the oral arguments regarding the Prometheus appeal on Dec. 7, 2011. Three months after hearing oral arguments, the Supreme Court issued its landmark decision invalidating the two Prometheus Labs patents on March 20.

Diagnostics Patentsin the Crosshairs

For medical diagnostic companies, the Prometheus decision potentially has far-reaching consequences. The Supreme Court’s decision could be used to invalidate broad patent claims and spur the renegotiation of royalties on licensed patents. In addition, the Prometheus decision could accelerate new developments in medical diagnostics if broad blocking patents are deemed invalid and removed as obstacles.

The patent claims in Prometheus were directed to diagnostic methods for determining patient-specific dosage of a drug. The Supreme Court’s decision likely will have wide implications for all companies attempting to develop assays for personalized medicine based on correlations between biomarkers and pathologies. In addition to methods for optimizing therapeutic efficacy of a drug, the Prometheus decision is likely to make it difficult to secure patent claims to diagnostic methods to determine a propensity of a patient to develop a disease based on the presence or absence of a genetic marker associated with the disease, as well as methods to diagnose a disease based on the presence of an abnormal level of a biomarker associated with the disease. Not being able to obtain patent protection for this innovative technology may have a chilling effect on commercialization of diagnostic assays that form the basis for personalized medicine.

Implications for Medtech

The impact of Prometheus already is being felt. Less than one week after the March 20 Prometheus decision, the Supreme Court addressed another much-watched patent case regarding the patentability of isolated DNA of human genes in Association for Molecular Pathology v. Myriad Genetics. On March 26, the Supreme Court granted certiorari, vacated the July 2011 Federal Circuit judgment upholding the patentability of isolated DNA patent claims, and remanded Myriad for further consideration in light of Mayo v. Prometheus. On July 20, the Federal Circuit will hear oral arguments in the much-anticipated Myriad case. Now, experts are lined up on both sides of the fence as to whether Myriad’s patents will be found to cover patentable subject matter or will be found invalid.

The district courts already have applied the Prometheus decision to several patent infringement cases across the country. On March 21, in Nazomi Communications Inc. v. Samsung Telecommunications, the District Court for the Northern District of California found that the Prometheus decision did not compel invalidating patent claims to methods of executing instructions in the telecommunications industry because these claims recited detailed steps that confined the claims to a specific, useful application.

An opposite result was found in Smartgene Inc. v. Advanced Biological Laboratories on March 30. In the Smartgene case, the District Court for the District of Columbia found that methods for selecting a therapeutic treatment regimen were directed to abstract ideas, and thus not patentable, because the patent claims simply recited abstract ideas in combination with “routine, conventional activity already engaged in by the scientific community.”

Finally, on March 21, one day after the Prometheus decision, the U.S. Patent and Trademark Office (USPTO) issued a memorandum to its patent examiners providing preliminary guidance regarding the Prometheus decision.

While these district court cases and the USPTO memorandum provide some early insight into the application of the Prometheus decision, the full impact of the decision will not be known for many years to come.

The Way Forward

The significance of the Supreme Court’s Prometheus decision for medical device and life-sciences companies depends on how broadly the lower courts interpret the Supreme Court’s mandate. Any patent claims reciting “laws of nature” could be impacted. All types of method claims could be affected, including methods of treatment, computer implementing methods, diagnostic methods and dosing methods. Even if granted claims look uncomfortably similar to Prometheus’ claims, all may not be lost and it may be possible to strengthen or uphold the validity of the patent.

In light of the landmark Prometheus decision, companies should take a number of steps to assess and strengthen their patent portfolios. Those steps include:

1. Conducting a patent audit. Companies should review their patent portfolios to assess any potential vulnerabilities given the new Prometheus playing field. Issued patents and pending patent applications need critical review to determine options for strengthening the portfolio.

2. Reviewing issued patents. Patent claims that cover novel applications of laws of nature, including delivery processes for personalized medicine, may be unaffected by Prometheus. However, patents that fall under the Prometheus umbrella may be strengthened through reissue or reexamination proceedings in the USPTO.

3. Positioning pending patent applications. Companies should review pending patents applications to see if the claims can be strengthened by adding additional transformative steps to the claims. Amending patent claims to recite novel “determining” steps may help overcome Prometheus. For example, claims can include steps of administering novel substances, steps that involve novel relationships between what is detected and a particular disease, or novel steps for administering or detecting a biological molecule.

4. A chilling effect on new patent application filings. While companies may think twice before filing a new patent application on diagnostic methods, more prudent approaches include claiming specific useful applications of natural laws and drafting claims that have a transformative step in the inventive limitation of the claims. The Supreme Court in Prometheus expressed concern that broad claims to laws of nature tie up the use of laws of nature and stifle innovation, even when the recited laws of nature are narrow and have only limited applications. Accordingly, to obtain patentable claims after Prometheus, the claims reciting a law of nature also should include unconventional, specific steps that transform the claimed method from one that preempts all use of the laws of nature into an inventive application of the natural law.

5. Following USPTO guidance. One day after the Prometheus decision, on March 21, the USPTO sent its Patent Examiners a memo offering “preliminary guidance” on how to apply the Prometheus ruling that requires rejection of patent applications directed to natural phenomena unless they include elements causing the claimed invention to amount to “significantly more” than a law of nature. The USPTO told patent examiners that the Prometheus ruling makes clear that: (1) because laws of nature, like the natural correlation between drug doses and toxin levels at issue in the Prometheus patents are not patent-eligible, methods related to such phenomena also are ineligible unless they include features that ensure the patent is a genuine application of those laws; (2) adding “conventional” steps with a high level of generality to natural phenomena cannot make those phenomena patent-eligible, and in order to be patent-eligible, a claimed invention must involve an application of such a law; and (3) “A claim that recites a law of nature or natural correlation, with additional steps that involve well-understood, routine, conventional activity previously engaged in by researchers in the field is not patent-eligible, regardless of whether the steps result in a transformation.” The USPTO plans to issue additional guidance on patent subject matter eligibility soon, and companies should strive to follow these USPTO guidelines.

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The unanimous Prometheus Supreme Court decision casts a dark cloud over diagnostics and personalized medicine patents. The full repercussions will not be known for many years. To build and maintain a strong patent portfolio in this uncertain environment, medtech companies need to pursue creative patent strategies that account for this major decision.

David J. Dykeman is co-chair of the Intellectual Property Department in the Boston, Mass.,
office of the international law firm Greenberg Traurig LLP. A registered patent attorney with more than 15 years of experience in patents, intellectual property and licensing, David’s practice focuses on securing strategic worldwide intellectual property protection and related business strategy for high-tech clients, with particular expertise in medical devices, life sciences, biotechnology and healthcare. David can be reached at (617) 310-6009 or dykemand@gtlaw.com. Roman Fayerberg is a registered patent attorney also located in Greenberg Traurig’s Boston office. Roman’s practice focuses on preparation and prosecution of patent applications and counseling clients on patent issues relating to medical devices,biomaterials, and nanotechnology. His patent practice builds on seven years of experience he gained as a research and development engineer at C.R. Bard and Boston Scientific Corp. Roman can be reached at (617) 310-5206 or fayerbergr@gtlaw.com.