In a case styled as In re BRCA1- and BRCA2-Based Hereditary Cancer Test Patent Litigation (also known as Myriad v. Ambry), the Federal Circuit held four of Myriad’s “primer” claims and two of Myriad’s detection method claims invalid for lack of subject matter eligibility under 35 USC § 101. The timing of this decision–coming two days after the USPTO’s Interim Guidance on subject matter eligibility which led many of us to believe that biotechnology inventions could be patented once again–makes it tempting to refer to the Federal Circuit as the Grinch Who Stole Christmas. But while the Grinch changed his mind just in time, it may take Congressional action before diagnostic and personalized medicine innovators have reason to celebrate.

The Patents At Issue

The patents at issue were Myriad’s U.S. Patent 5,753,441, U.S. Patent 5,747,282, and U.S. Patent 5,837,492, which are directed to the BRCA1 and BRCA2 genes associated with breast cancer and ovarian cancer. While these patents previously were before the Supreme Court, the specific claims at issue in this case were not.

Claim 16 of the ’282 patent was representative of the “primer” claims:

16. A pair of single-stranded DNA primers for determination of a nuycleotide [sic] sequence of a BRCA1 gene by a polymerase chin [sic] reaction, the sequence of said primers being derived from human chromosomne sic] 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.

Claim 7 of the ’441 patent was representative of the “method” claims:

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.

(Rewritten in independent form in accordance with the Federal Circuit decision.)

As noted in the Federal Circuit decision, after the Supreme Court invalidated some of Myriad’s claims, Ambry entered the market with a kit for diagnosing ”susceptibility to particular kinds of cancer.” Myriad sued for infringement of “sixty-six claims across fifteen different patents,” and sought a preliminary injunction based on the six claims at issue in this appeal. In a decision I wrote about here, the district court denied Myriad’s motion for a preliminary injunction, finding that Ambry had “raised a substantial question concerning … subject matter eligibility,” such that Myriad had not established a likelihood of success on the merits, and so was “not entitled to a preliminary injunction at this time.”

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Dyk and joined by Judges Prost and Clevenger.

The Primer Claims

The Federal Circuit addressed the primer claims first, and found them to lack subject matter eligibility under the Supreme Court decision in Myriad:

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. Primers necessarily contain the identical sequence of the BRCA sequence directly opposite to the strand to which they are designed to bind. They are structurally identical to the ends of DNA strands found in nature.

The Federal Circuit rejected Myriad’s arguments that the primers satisfied §101

  • because they were made synthetically:

As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible.

  • because single-stranded DNA is not found in the human body:

[A]s the Supreme Court made clear, “separating [DNA] from its surrounding genetic material is not an act of invention.”

  • because they have a “fundamentally different function ….as a starting material for a DNA polymerization process”:

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.

What about a fundamentally different utility in a diagnostic method?

A DNA structure with a function similar to that found in nature can only be patent eligible as a composition of matter if it has a unique structure, different from anything found in nature.

The Method Claims

The Federal Circuit’s analysis of the method claims is more difficult follow (and perhaps more difficult to swallow?). Although Ambry had argued that the claims should be held ineligible under the Supreme Court decision in Mayo v. Prometheus “because … [they] simply identify a law of nature … and apply conventional techniques,” the Federal Circuit rendered its decision under the Supreme Court’s more recent decision in Alice:

We need not decide if Mayo is directly on point here because the method claims before us suffer from a separate infirmity: they recite abstract ideas.

The Federal Circuit considered the first and second paragraphs of the method claims separately:

Here, we treat separately the first paragraphs of claims 7 and 8, which describe the comparison of wildtype genetic sequences with the subject’s genetic sequence and correspond to the first step of Alice, and the second paragraphs, which describe the techniques to be used in making the comparisons and correspond to the second step of Alice.

(In the actual patent, the “first paragraph” is the language of claim 1, while the “second paragraph” is the language of claim 2. Perhaps a single claim written as a single paragraph would have been more difficult to parse into “ineligible” and “not enough more” parts?)

[T]he comparisons described in the first paragraphs of claims 7 and 8 are directed to the patent-ineligible abstract idea of comparing BRCA sequences and determining the existence of alterations.

*****

Having determined that the comparison steps of claims 7 and 8 are abstract ideas, we move to the second step of Alice and ask whether the particular mechanism for the comparisons added by claims 7 or 8 renders the claims patent-eligible. …. [Under Alice, t]here must be a further inventive concept to take the claim into the realm of patent-eligibility.

*****

The second paragraphs of claims 7 and 8 do nothing more than spell out what practitioners already knew—how to compare gene sequences using routine, ordinary techniques.

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.

Thus, the Federal Circuit determined that “[t]he claims on appeal are directed to ineligible subject matter in violation of 35 U.S.C. § 101,” affirmed the district court’s denial of Myriad’s motion for preliminary injunction, and awarded costs to Ambry.

Would Narrower Method Claims Have Fared Better?

In analyzing the method claims, the Federal Circuit commented on their breadth, and noted that they were not limited to detecting specific mutations, or to any specific purpose:

The number of covered comparisons is unlimited. The covered comparisons are not restricted by the purpose of the comparison or the alteration being detected. Because of its breadth, the comparison step covers detection of yet undiscovered alterations, as well as comparisons for purposes other than detection of cancer. Even with respect to cancer, the comparisons are not limited to the detection of risk of breast or ovarian cancer. Similar concerns to the ones the Supreme Court expressed in Myriad with respect to isolated DNA exist here: allowing a patent on the comparison step could impede a great swath of research relating to the BRCA genes, and it is antithetical to the patent laws to allow these basic building blocks of scientific research to be monopolized.

Innovators and practitioners may want to study this portion of the court’s decision, and determine if their diagnostic or personalized medicine method claims can be distinguished, such as by reciting the detection of specific markers for a specific purpose.