On October 6, 2014, the Federal Circuit heard oral arguments in a case involving the claims of the Myriad gene patents that were not invalidated by the Supreme Court’s 2013 decision. The Federal Circuit is reviewing the district court’s denial of Myriad’s motion for a preliminary injunction against Ambry Genetics Corp., based on the finding that Ambry had “raised a substantial question” as to whether Myriad’s “Primer Claims” and “Method Claims” are directed to “patent [in]eligible products of nature and abstract ideas.” (You can read more about the district court decision here.) The easiest decision for the Federal Circuit to reach would be to affirm based on the “substantial question” standard without deciding patent eligibility on the merits. As Myriad’s counsel suggested, such a decision would leave the biotech industry “at sea” until the case makes it way back to the Federal Circuit again.

The Myriad Claims At Issue

The district court divided the Myriad gene patent claims at issue into the Primer Claims and the Method Claims.

The Primer Claims included claims 16 and 17 of U.S. Patent No. 5,747,282 and claims 29 and 30 of U.S. Patent No. 5,837,492.  Claims 16 and 17 of the ’282 patent are representative.

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.

 17. The pair of primers of claim 16 wherin [sic] said BRCA1 gene has the nucleotide sequence set forth in SEQ ID NO:1.

The claimed primers have nucleotide sequences that correspond to fragments of the naturally occurring BRCA1 and BRCA2 sequences. As such, these claims would not be patent eligible under the USPTO’s March 4, 2014 Patent Subject Matter Eligibility Guidance.

The Method Claims included claims 7 and 8 of U.S.Patent No. 5,753,441, claim 4 of U.S. Patent No. 6,033,857, claim 5 of  U.S. Patent No. 6,951,721, and claims 2 and 4 of U.S. Patent No. 5,654,155. Claim 4 of the ’857 patent is representative:

4. The method of claim 2 wherein the detection in the alteration in the germline sequence is determined by an assay selected from the group consisting of (a) observing shifts in electrophoretic mobility of single-stranded DNA on non-denaturing polyacrylamide gels, (b) hybridizing a BRCA2 gene probe to genomic DNA isolated from said tissue sample, (c) hybridizing an allele-specific probe to genomic DNA of the tissue sample, (d) amplifying all or part of the BRCA2 gene from said tissue sample to produce an amplified sequence and sequencing the amplified sequence, (e) amplifying all or part of the BRCA2 gene from said tissue sample using primers for a specific BRCA2 mutant allele, (f) molecularly cloning all or part of the BRCA2 gene from said tissue sample to produce a cloned sequence and sequencing the cloned sequence, (g) identifying a mismatch between (1) a BRCA2 gene or a BRCA2 mRNA isolated from said tissue sample, and (2) a nucleic acid probe complementary to the human wild-type BRCA2 gene sequence, when molecules (1) and (2) are hybridized to each other to form a duplex, (h) amplification of BRCA2 gene sequences in said tissue sample and hybridization of the amplified sequences to nucleic acid probes which comprise wild-type BRCA2 gene sequences, (i) amplification of BRCA2 gene sequences in said tissue sample and hybridization of the amplified sequences to nucleic acid probes which comprise mutant BRCA2 gene sequences, (j) screening for a deletion mutation in said tissue sample, (k) screening for a point mutation in said tissue sample, (l) screening for an insertion mutation in said tissue sample, (m) in situ hybridization of the BRCA2 gene of said tissue sample with nucleic acid probes which comprise the BRCA2 gene.

The claimed methods “involve” a product of nature. As such, their patent eligibility under the USPTO’s Guidance would depend on the outcome of the multi-factored analysis laid out in the Guidance.

The Oral Arguments

The appeal has been assigned to a panel consisting of Chief Judge Prost, Judge Clevenger and Judge Dyk. Jonathan Singer from Fish and Richardson P.C. argued for Myriad. Counsel for Ambry did not identify himself on the record, but William Gaede, III from McDermott Will & Emery LLP is named as the lead attorney on the Ambry briefs.

The following is a rough summary of key questions and answers based on my review of the oral argument recording that you can find here.

Judge Prost: Is it your position that you should look at the entire claim? I thought the Supreme Court was quite clear in Myriad: You take away the abstract idea or law of nature, look at the additional steps, and determine whether the additional steps are well-understood, routine, and conventional such that they add nothing significant.

Judge Clevenger: Walk me through “the claim as a whole” analysis ….

Judge Dyk: How does adding conventional steps confer patentability?

Myriad: The BRCA1 probe was not conventional. The BRCA1 probe is part of the invention and had never been used before. …. Myriad did not invent how to make cDNA from a genomic sequence, but the Supreme Court held that the cDNA sequence was patent eligible. The Supreme Court did not hold that you have to invent a new method of making cDNA in order for a cDNA sequence to be patent eligible.

Myriad: The Primer Claims have a utility that is different from what’s found in nature–a utility in PCR. That distinguishes them from the bacteria at issue in Funk Brothers.

Judge Clevenger: Isn’t the issue before us whether there is a “substantial question” of patent eligibility?

Judge Dyk: Would a district court trial illuminate the issues before us?

Myriad: The main issues are issues of law. …. The biotech community is at sea, and this case is a good one to resolve these issues.

Ambry: A primer is just a segment of DNA, and the Supreme Court held in Myriad that when cDNA is indistinguishable from genomic DNA, it is not patent eligible.

Judge Clevenger: What do primers do in the body? Don’t they have a different function?

Ambry: RNA primers help prime the synthesis and replication of DNA and RNA. The district court found that primers perform the task of priming in a way that mirrors and mimics nature –they form the starting point of filling in of subsequent nucleotides of the second strand of DNA.

Judge Dyk: What difference is there if the function is different? That’s true in all of the claims that we considered the first time around. When you take a part of the DNA you’re going to use it for different functions–for comparisons, for example. …. Function can’t be the test, can it? All the other claims would have come out differently–so function can’t be the determinant.

Ambry: All other steps in the claims were routine and conventional

Judge Dyk: Do you see a difference between claim 7 and 8 and claim 21 [which was upheld]?

Judge Clevenger: Was the probe new?

Ambry: The Primer Claims are not patent eligible because they are a product of nature, as a segment of naturally occurring DNA.

Judge Clevenger: If the probe were tagged [labeled] would it be eligible?

Ambry: I don’t think so.

Judge Clevenger: What can your adversary patent?

Ambry: As discussed in Alice, they could obtain a patent if there was an improvement in the function of the primer or probe over the prior art, or an advancement in the technology.

Judge Dyk: The Supreme Court was concerned about excluding all possible claims that would reward the invention here.

Ambry: They do have claim 21, to the method of using the sequence in an in vitro assay, where there is a new construct made, as in Chakrabarty.

Myriad: Myriad did not invent the basic technique of claim 21, so that can’t be the basis for eligibility. The Primer Claims represent an enlargement of utility, which was lacking in Funk Brothers, and which should support eligibility.

Biotech At Sea

If the biotech industry has been at sea since the 2013 Supreme Court decision in Myriad, it might feel storm-tossed after these oral arguments. I’m not sure if I’m more worried about Judge Prost’s summary of Myriad‘s clear directions to consider the claims as a whole by picking them apart, or by Judge Dyk’s conviction that a different function can’t be the basis for eligibility. Instead of hoping for a rescue at sea, I am left worrying that the biotech industry will be walking the plank after this latest Myriad gene patents case.