On December 17, 2014, the Federal Circuit Court of Appeals found that certain claims relating to Myriad’s BRCA1 genetic test for breast and ovarian cancer were invalid under 35 U.S.C. § 101 as being ineligible for patent protection. The claims at issue were directed to DNA primers that could be used to detect mutations in the BRCA1 gene and methods for screening for germline alterations in the BRCA1 gene. The court based its analysis on the Supreme Court decisions Association for Molecular Pathology v. Myriad, 133 S. Ct. 2107(2013) (“Myriad”) and Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) (“Alice”). The Federal Circuit analyzed the composition claims and the method claims under different frameworks

Initially, the court focused on the composition claims, which were directed to

A pair of single-stranded DNA primers for determination of a nucleotide sequence of a BRCA1 gene by a polymerase chain reaction, the sequence of said primers being derived from human chromosome 17q, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA having all or part of the sequence of the BRCA1 gene.

The Federal Circuit explained that the “analysis of the primer claims under § 101 is guided by the Supreme Court’s Myriad decision.” The Federal Circuit began by summarizing the Myriad decision, which held that isolated DNA sequences are not patentable because they could be found in nature, but cDNA sequences are patent eligible because such sequences are not found in nature. Under this framework, the Federal Circuit found that DNA primers are analogous to the isolated DNA. “The primers before us are not distinguishable from the isolated DNA found patent-ineligible in Myriad and are not similar to the cDNA found to be patent-eligible” because the primers “are structurally identical to the ends of DNA strands found in nature.”

Myriad had argued that the primers are different because they are synthetically replicated. The Federal Circuit dismissed this argument, in part, because the creation of such DNA by synthetic means is routine. Myriad also argued that the primers are not naturally occurring because “single-stranded DNA cannot be found in the human body.” But, according to the opinion, this is not enough to create patentable eligible subject matter. “Separating [DNA] from its surrounding genetic material is not an act of invention.”

Myriad also argued that the primers are patentable because they have a different function from the sequences found in nature. According to the opinion, Myriad argued that,

When part of the naturally occurring genetic sequence, DNA “stores the biological information used in the development and functioning of all known living organisms,” but when isolated as a primer, the DNA fragment “prime[s], i.e., . . . serve[s] as a starting material for a DNA polymerization process.

The Federal Circuit disagreed. “In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function.” The court continued to explain:

Rather, the naturally occurring material is used to form the first step in a chain reaction—a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here—the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.

For the primer to be eligible for patent protection under 35 U.S.C. § 101 it must have a different structure, or by implication, a “significantly new function.” Therefore, the claims directed to the primers were found to be patent ineligible.

The Federal Circuit’s decision then focused on the method claim. The method claim recited:

A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject[,]

wherein a germline nucleic acid sequence is compared by hybridizing a BRCA1 gene probe which specifically hybridizes to a BRCA1 allele to genomic DNA isolated from said sample and detecting the presence of a hybridization product wherein a presence of said product indicates the presence of said allele in the subject.

The court analyzed the claims under the two-step framework set forth in the recent Supreme Court Alice decision. As explained by the Federal Circuit, this entails asking two questions. “First, ‘we determine whether the claims at issue are directed to [a] patent-ineligible concept. If so, we then ask, ‘what else is there in the claims before us?’” “Put another way, there must be a further ‘inventive concept’ to take the claim into the realm of patent eligibility” if the answer to the first question is “yes.”

In its analysis, the court broke the method claim into two parts, focusing the first question on the first paragraph of the method claim and the second question on the second paragraph. The court held that the first question regarding the first paragraph had already been answered in a previous case. Therefore, for the claim to survive under 35 U.S.C. § 101 the second paragraph of the claim must add a “further inventive concept.” The court found that the elements in the second paragraph of the claim “do not add ‘enough’ to make the claims as a whole patent-eligible.” The court explained that the second paragraph does not add anything new. “Nothing is added by identifying the techniques to be used in making the comparison because those comparison techniques were the well-understood, routine, and conventional techniques that a scientist would have thought of when instructed to compare two gene sequences.”

Myriad had argued that the method claim should be patentable because it is similar to claim that the Federal Circuit had implied would be patent eligible. However, the Federal Circuit indicated that the claim referenced by Myriad was not at issue in the previous decision so the previous decision has no precedential effect. However, even if it has been found to be patent eligible the court explained that the claim at issue in this case was significantly different. The court explained that the method claim from the previous opinion recited specific mutations to be analyzed. In contrast, the claims in the present case “are significantly broader and more abstract, as they claim all comparisons between the patient’s BRCA genes and the wildtype BRCA genes.” Therefore, the claims are directed to “abstract comparisons” and the rest of the claim recites “only routine and conventional steps.” Therefore, the method claims are also ineligible for patent protection under 35 U.S.C. § 101.

This decision puts at risk many biotech patents relating to naturally occurring products and diagnostics. Claims directed to methods of diagnosis will have to be reevaluated in view of yesterday’s decision. The opinion’s holding regarding DNA primers will also have implications regarding claims directed to naturally occurring products and their uses. This decision comes on the heels of the United States Patent and Trademark Office (USPTO) issuing its revised guidance for examiners on how to evaluate whether a claim is eligible for patent protection under 35 U.S.C. § 101. The USPTO guidance is mostly consistent with this opinion, however, the Federal Circuit’s analysis of the primers and the relationship between their function in nature and their function in the invention may require the USPTO to further revise its interim guidance. A further update will be forthcoming regarding the USPTO guidance and its implications.

A copy of the Federal Circuit’s decision may be found here.