Share

Diagnosing the Sequenom Problem

Article
07.05.2016
By Steve Kazmierski and Samir Mehta

This article was published in Law360 on July 1.

On June 27, in a closely watched case, the U.S. Supreme Court denied a petition to review decisions by lower courts that invalidated a patent in the field of diagnostic biotechnology. However, by denying Sequenom's petition from the Federal Circuit's ruling in Ariosa Diagnostics Inc. v. Sequenom Inc., the Supreme Court has left the field of diagnostic biotechnology in a state of limbo, which began with the Supreme Court's 2012 decision in Mayo Collaborative v. Prometheus Labs. Since the Mayo decision, corporations, researchers and universities that have discovered novel diagnostic techniques have had little certainty that their discoveries could be eligible for patent protection. And as a result, for the past four years, inventors of groundbreaking technologies worth billions of dollars in the biotechnology industry have been unable to obtain or enforce patent rights. That said, denying Sequenom's petition was the right thing to do because of the specific claims at issue — even if it means the biotechnology industry will have to wait longer to get out of limbo.

The key to the Supreme Court's ruling in the Mayo decision, and to the Federal Circuit's ruling in Ariosa, is the application of 35 USC § 101. The motivation of the Supreme Court was to prevent inventors from monopolizing an entire industry that ties to a particular law of nature, natural phenomena or abstract idea. The court voiced a concern that such monopolies, "through the grant of a patent might tend to impede innovation more than it would tend to promote it." However well intentioned, the practical effect of Mayo and subsequent cases has been to deny patent eligibility to inventions, particularly in the fields of diagnostics and computer software. As a result, patent attorneys and their clients have been left adrift when trying to protect and enforce diagnostic and software intellectual property.

Why do diagnostic claims face such an uphill battle? As a practical matter, all diagnostic biotechnology patent applications are necessarily directed towards a law of nature or a natural phenomenon. (Try presenting an argument that discoveries tied to human biology do not relate to a law of nature. Good luck.) More troublingly, neither the courts nor the U.S. Patent and Trademark Office in its guidance has identified what can constitute eligible subject matter in the context of a diagnostic patent claim.

Given the importance of diagnostic inventions, this state of affairs has been a source of frustration and debate within the biotechnology industry. Indeed, the Supreme Court denied Sequenom's petition despite the fact that over 20 amicus briefs were filed urging the court to take the case up. If the law is in such a state of flux, and industry is frustrated, why not clarify the patent-eligible subject matter standard? Perhaps the Sequenom claims gave the court no anchor point onto which it could attach a meaningful opinion.

The lower courts found that the Sequenom claims were not patent-eligible — and rightfully so using the Mayo analysis. The claims were not patent-eligible because, among other things, the claims do nothing more than "detect" a naturally occurring phenomenon. Claim 1 recites:

A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises:
amplifying a paternally inherited nucleic acid from the serum or plasma sample and
detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

Rather than analyzing claims 1 and 21 under § 101 to conclude that they are directed to a patent-ineligible natural law, the lower courts could have disposed of claims 1 and 21 of the Sequenom patent using statutory provisions such as §§ 102, 103 and/or 112 — but they did not.

For instance, the patentability of claim 1 can be analyzed for novelty and nonobviousness. It is undisputed that the presence of cell-free fetal DNA in maternal blood is novel. So the question remains whether amplifying cffDNA is obvious following a § 103 analysis. Amplifying DNA from serum or plasma samples appears to be well known and routine. Thus, the obviousness answer turns on whether the novelty of the presence of cffDNA is enough to warrant a finding that the claim is nonobviousness.

Claim 21 depends from claim 1, and recites:

A method of performing a prenatal diagnosis, which method comprises the steps of:
(i) providing a maternal blood sample;
(ii) separating the sample into a cellular and a non-cellular fraction;
(iii) detecting the presence of a nucleic acid of foetal origin in the non-cellular fraction according to the method of claim 1;
(iv) providing a diagnosis based on the presence and/or quantity and/or sequence of the foetal nucleic acid.

The detecting step of claim 21 recites "a nucleic acid of foetal origin", which presents antecedent and indefiniteness issues. Does "a nucleic acid of foetal origin" refer to a paternally inherited nucleic acid, "a paternally inherited nucleic acid of fetal origin", or to a third type of nucleic acid? Is the nucleic acid of foetal origin amplified according to the amplifying step or detected according to an unrecited detecting method?

Arguably, the "providing a diagnosis" phrase triggered the § 101 analysis, resulting in the patent ineligibility conclusion, and ultimately causing the denial of cert. Even the diagnosing step could more easily have been addressed using the other statutory provisions — which was precisely the point many amici made in their briefs.

Indeed, to explain the diagnosis step, one must turn to the specification. Notably, the preamble of claim 21 recites, "[a] method of performing a prenatal diagnosis" and the only diagnosing limitation recites, "providing a diagnosis based on the presence and/or quantity and/or sequence of the foetal nucleic acid." The claim itself does not recite what type of prenatal diagnosis is made. The specification, however, recites many uses such as sex determination, paternally inherited polymorphisms or mutations, Down syndrome and other chromosomal aneuploidies, and placental pathologies.

At the end of the day, this claim set may not have been the right one for the court to consider. It would have involved a complex analysis of the deficiencies of the claims and, to be a meaningful decision, the court would nevertheless need a motivation to revise its prior decisions. Ariosa was apparently not the right case. (It is worth noting that both Mayo and Alice Corp. v. CLS Bank International, which applied Mayo's holding to the field of software were unanimous decisions. There may have been little desire for such a like-minded court to revisit this issue.)

Yet, even though Sequenom's petition was denied, the courts must return to this question, and soon. The biotechnology industry is at a crossroads and requires better direction than the courts have provided. What might a better case look like for clarification?

As indicated above and in the USPTO guidelines, "diagnosis" is the key claim term that triggers the Mayo analysis and ultimately renders the claim unpatentable. To take the USPTO's strained example, a claim reciting the detection of a biomarker is identified as being patent eligible, yet adding a "diagnosing" step to the exact same claim and all of those previous steps suddenly become "well-understood, routine, and conventional activity" and the "diagnosing" step transforms the claim into an abstract idea.

As an initial matter, it would help to recognize that diagnostic claims, as a whole, are typically directed to an assay that uses a variety of reagents to perform the steps. The natural principle is that a biomarker level fluctuates because of a disease. Identifying that correlation necessarily requires human intervention. There would not be any reason to determine a biomarker level for any case unless someone discovered that the biomarker level correlated with a disease. But, the courts and the USPTO have decided that correlating a biomarker with a disease is a natural principle.

Therefore, the claim must do more, which is where the requirement of practically applying the correlation should be enough to satisfy the eligibility question. If one discovers that a high concentration of biomarker X correlates with a disease, and the claims require determining the concentration in a sample obtained from a patient, and then providing a diagnosis that the person has or does not have the disease based on the biomarker X level detected by performing the method should represent the practical application. Simply dismissing a diagnosis step as a thought ignores all of the other steps recited in the claim and places inappropriate weight on a single step.

The best challenge to the Mayo framework will be a well-defined set of claims that have no major novelty, obviousness, or indefiniteness issues that is clearly limited to diagnostics. Yet, in order to force this issue to the Federal Circuit, clients and attorneys need to continue to be aggressive about their patent applications. We suggest that you vigorously prosecute and appeal 35 USC § 101 rejections to strong diagnostic applications. Sequenom may have lost its petition, but somebody will make case law in the future. That somebody may be you.

Subscribe to Stinson's
News & Insights
Jump to Page

We use cookies on our website to improve functionality and performance, analyze website traffic and enable social media features. By continuing to use our website, you agree to our use of cookies. For more information, please see our Cookie Policy.