The Diagnostics Dilemma: Securing and Protecting Diagnostic-Based Claims

While many life sciences companies are built on platforms involving the development of diagnostic products and methods that underlie personalized medicine allowing treatment that is customized to a patient’s unique biology, the U.S. Supreme Court dealt a blow to the industry with its decision in Mayo Collaborative Services v. Prometheus Laboratories.[1]  This decision, along with subsequent court decisions, has rendered certain subject matter patent ineligible under 35 U.S.C. §101 if it exploits laws of nature or natural phenomena, cornerstones of the diagnostic industry.  Although novel diagnostic agents should be patent eligible, uncertainty remains about certain diagnostic-based method claims that rely on a correlation between a diagnostic biomarker and a disease or indication. 

A recent draft bill released by bipartisan members of Congress offers promise of legislative action that may restore broad patent eligibility to diagnostics.[5/24 Blog Post]  Until then, recent decisions by the Federal Circuit, including Vanda Pharmaceuticals Inc. vs. West-Ward Pharmaceuticals International [3] and Endo Pharmaceuticals Inc. v. Teva Pharmaceuticals USA,[4] have provided some clarity on the reach of patent eligible subject matter to diagnostic method claims.  Although these decisions may open the door to issuance and validity of a patent to diagnostic methods, the Court’s decision in Cleveland Clinic Foundation v. True Health Diagnostics[5] underscores the reality that certain diagnostic-type claims may not provide adequate protection against potential infringers.  For this reason, companies should work with patent counsel to ensure that they secure patent-eligible claims to diagnostic methods and related treatments that are of defendable commercial value.

Subject Matter Eligibility of Diagnostic Claims Under 35 § USC 101

As part of its landmark Alice Corp. v. CLS Bank International decision, the Supreme Court articulated a two-step framework for determining whether claims are patent eligible.[6]  In the first step, it must be determined whether a claim is directed to a judicial exception (a law of nature, a natural phenomenon, or an abstract idea).  If so, it must then be determined whether the elements of the claim, individually or as a whole, “transform the nature of the claim into a patent-eligible application.”[7]  As Mayo explained, adding “conventional steps, specified at a high level of generality” to a law of nature does not make a claim patentable.  However, subject matter that includes “additional features that provide practical assurance that the processes are genuine applications of those laws rather than drafting efforts designed to monopolize the correlations” may be patent eligible.[8]

After a long line of decisions finding many diagnostic-based claims to be patent ineligible under Section 101, the Federal Circuit has recently found certain types of diagnostic method claims to be patent eligible.  In Vanda Pharmaceuticals, the claim at issue was directed to the identification of a genetic variant that renders individuals poor metabolizers of a compound used to treat schizophrenia, and administering specific and different amounts of the compound to individuals, depending on whether they harbored the genetic variant.  Similarly, in Endo Pharmaceuticals, the claims were directed to treating pain in a renally impaired patient with a compound, wherein the creatinine clearance rate of the patient was measured, and a lower dosage of the compound was administered to the patient, depending on the patient’s rate of creatinine clearance.  The Court found the claims at issue in these two cases to be patent eligible, as being directed to “a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.”[9]

This is contrast to the recent Federal Circuit decision in Athena Diagnostics vs. Mayo Collaborative Services.[10]  There, a claim reciting a method of diagnosing disorders related to muscle specific tyrosine kinase (MuSK) that only included a step of detecting autoantibodies to an epitope of MuSK was deemed to be patent ineligible because it did not sufficiently transform a law of nature into a patent-eligible application of the law, as required by the original Mayo decision.

In response to the Federal Circuit’s evolving jurisprudence, the PTO published revised subject matter eligibility guidelines in January 2019.[11]  The new guidelines explain that a “claim that recites a judicial exception is not ‘directed to’ the judicial exception if the judicial exception is integrated into a practical application of the judicial exception.”  To this end, the PTO guidelines explain that a claim reciting a practical application of a judicial exception is patent eligible at step one of the Alice/Mayo test.  In this way, both the revised PTO guidelines and the Federal Circuit decisions have provided some clarity that is in line with the initial guidance provided by Mayo.

While the courts have clarified how patent applicants may overcome the subject matter eligibility hurdle to secure patents to diagnostic-type claims, integrating a “practical application” into a diagnostic method claim may require reciting a series of steps to apply a natural correlation involving a biomarker, such as detecting the biomarker in a sample, diagnosing a patient as having a disease or condition related to the biomarker, and treating the patient with an appropriate therapeutic.  Such multi-step processes may be carried out by multiple entities.  It’s easy to imagine that the first step would be carried out by a diagnostic company, while the latter two steps would be carried out by a physician.

Thus, even if the patent eligibility hurdle is overcome, these same applicants may face an additional obstacle when they seek to enforce their patents against multiple potential infringers.  Specifically, patent owners may be required to prove induced infringement, which has additional evidentiary burdens beyond those required to prove direct infringement by a single actor.

Proving Infringement by Multiple Actors

Where multiple actors are alleged to infringe different steps of a patent claim, plaintiffs commonly must assert a theory of induced infringement.  That is, a plaintiff alleges that a defendant infringed some steps of a claim and induced another actor to infringe the other steps of the claim, or the defendant induced another actor to infringe all steps of the claim.  To prevail on a claim of induced infringement, however, a plaintiff must prove that the defendant had the specific intent to induce another party to infringe.  Additionally, induced infringement must be predicated on direct infringement.[12]  When multiple parties carry out different steps of a method, direct infringement is shown by a single defendant controlling or directing the actions of the other defendant(s), such that all actions are attributable to a single defendant.[13]  Directing or controlling another’s actions is demonstrated by (1) conditioning participation in an activity or receipt of a benefit upon performance of a step or steps of a claimed method and (2) establishing the manner or timing of that performance.[14]  

Recent Federal Circuit cases highlight the potential difficulty of proving induced infringement of a multi-step method claim.  In Cleveland Clinic, the Cleveland Clinic Foundation (“CCF”) owned a method of treatment patent reciting multiple steps that were alleged to be separately carried out by True Health, a diagnostic company, and physicians. CCF sued True Health on an induced infringement theory, but lost as a result of not being able to provide factual support showing that True Health specifically intended to induce the physicians to infringe the patent at issue by diagnosing and treating patients.[15] 

In contrast, in the Eli Lilly and Co. v. Teva Parenteral Medicines case, the method claim included a step of administering a pretreatment and another step of administering a treatment. There, the plaintiff was able to show that the defendant induced infringement, as its product labeling instructed physicians to condition a patient’s receipt of treatment on the patient self-administering the pretreatment at specific doses and times.[16]  Vanda was also able to prove induced infringement of its multi-step method claim against the generic manufacturer West-Ward based on general language on West-Ward’s product label that the dose of the drug should be reduced in half if the patient is a poor metabolizer.[17]  A difference between Cleveland Clinic and cases in which induced infringement was found is the development of the factual record supporting the inducing activity, particularly as highlighted by language on a product label. 

Conclusion

Clients seeking patents related to personalized medicine should pursue claims that both comply with patent eligibility requirements and mitigate evidentiary burdens for finding induced infringement.  Drafting claims that capture a practical application of a natural correlation, but in a form that would be infringed by a single actor, may reduce the factual inquiries necessary to prove infringement, as compared to claims requiring multiple actors.  Further, a patent strategy should coordinate the language of patent claims to what may be on a product label, particularly because many potential infringers, including generic manufacturers, may practically implement similar instructions on their product label.


[1] Mayo Collaborative Servs. v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012).

[5/24 Blog Post] https://lifesciences.mofo.com/topics/congress-bipartisan-bill-on-patent-eligibility.html

[3] Vanda Pharmaceuticals, Inc. v. West-Ward Pharmaceuticals Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018).

[4] Endo Pharmaceuticals Inc. v. Teva Pharmaceuticals Inc., 919 F.3d 1347 (Fed. Cir. 2019).

[5] Cleveland Clinic Foundation v. True Health Diagnostics LLC,  859 F.3d 1352 (Fed. Cir. 2017)

[6] Alice Corp. Ptd. Ltd. V. CLS Bank Int’l, 573 U.S. 208, 217-18 (2014).

[7] Id. at 217.

[8] Mayo at 82.

[9] Endo at 1354.

[10] Athena Diagnostics, Inc. v Mayo Collaborative Servs., LLC, 915 F.3d 743 (Fed. Cir. 2019).

[11] https://federalregister.gov/d/2018-28282

[12] Limelight Networks, Inc. v. Akamai Techs., Inc., 572 U.S. 915, 920-21 (2014).

[13] Id.

[14] Eli Lilly and Co. v. Teva Parenteral Medicines, Inc., 845 F.3d 1357, 1364-79 (Fed. Cir. 2017).

[15] Cleveland Clinic at 1364.

[16] Eli Lilly at 1369.

[17] Vanda at 1130-31.