By Kevin E. Noonan --
In a decision that will surprise no one (written by Judge Dyk, which made the conclusions foregone from the first page of the opinion), the Federal Circuit today affirmed the Utah District Court's decision denying Myriad Genetics' motion for a preliminary injunction in the consolidated Multidistrict Litigation styled In re BRCA1- and BRCA2-based Hereditary Cancer Test Patent Litigation. What might have been anticipated but is still surprising is the opinion's apparent willingness to ignore established patent law principles (and the statute) in favor of obsequious obedience to what the panel perceives to be Supreme Court precedent while at the same time ignoring Myriad's arguments that relied upon express language from the Court's recent § 101 cases.
To recap, the appeal was over the following claims from Myriad's asserted patents (in a footnote the opinion noted that Myriad was no longer pursuing an appeal with regard to claims 2 and 4 of U.S. Patent No. 5,654,155, claim 5 of U.S. Patent No. 6,951,721, and claim 4 of U.S. Patent No. 6,033,857).
From U.S. Patent No. 5,753,441 ("the '441 patent"):
7. 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 [The method of claim 1] 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.
8. 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 [The method of claim 1] wherein a germline nucleic acid sequence is compared by amplifying all or part of a BRCA1 gene from said sample using a set of primers to produce amplified nucleic acids and sequencing the amplified nucleic acids.
(where claim language in italics recites limitations from the independent claim, and language in bold and italics is relevant to the Court's opinion).
From U.S. Patent No. 5,747,282 ("the '282 patent"):
16. 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 chromosomne 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 wherein said BRCA1 gene has the nucleotide sequence set forth in SEQ ID NO:1.
From U.S. Patent No. 5,837,492 ("the '492 patent"):
29. A pair of single-stranded DNA primers of at least 15 nucleotides in length for determination of the nucleotide sequence of a BRCA2 gene by a polymerase chain reaction, the sequence of said primers being isolated from human chromosome 13, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA comprising all or at least 15 contiguous nucleotides of the BRCA2 gene.
30. The pair of primers of claim 29 wherein said BRCA2 gene has the nucleotide sequence set forth in SEQ ID NO:1.
Myriad moved in the District Court for a preliminary injunction, which the Court denied; while it found that Myriad had established the required risk of irreparable harm, the public interest was "in equipoise" and the balance of the hardships tipped slightly in Ambry's favor. The Court denied the injunction because it found Myriad had not demonstrated a likelihood of success on the merits, based on its application of the Supreme Court's Myriad decision in determining that the asserted claims were invalid for failure to recite patent-eligible subject matter.
The Federal Circuit's opinion was written by Judge Dyk, joined by Chief Judge Prost and Judge Clevenger. The Court performed its invalidity assessment on the composition of matter claims from the '282 and '492 patents separately from its analysis of the '441 patent's method claims, with the Supreme Court's prior opinion on the validity of other claims from these patents casting a determinative shadow on the opinion. The panel's characterization of the Myriad opinion set the stage:
The Supreme Court, in its Myriad decision, held that claims of the '282 patent directed to isolated DNA were drawn to patent-ineligible subject matter because the isolated DNA strands, which are naturally occurring and separated from the rest of the human genome, were natural phenomena.
For these composition of matter claims, and using claim 16 of the '282 patent as being representative and further being "guided by [the Supreme Court's] Myriad [decision]" the Court analogized the claimed primers to genomic DNA (based on no asserted change in sequence) and rejected Myriad's attempts to distinguish based on their synthetic nature. With little explanation of what the panel thought its statements meant as a factual matter, the opinion stated that its earlier Myriad opinion had established that DNA fragments are "synthesized" in nature as well as by man, neglecting the distinction between the claimed single-stranded oligonucleotides (ssDNA) and "naturally occurring" double stranded DNA fragments. In a pattern that returns with even more force in the method claims, the opinion notes the breadth of the claimed primers, which can be any short DNA molecules that hybridize to any portion of the BRCA1 or BRCA2 genomic DNA. It will be appreciated that Myriad's own claim language was helpful in reaching this conclusion, insofar as claim 16 recites "said primers being derived from human chromosomne 17q" and that "the primers support PCR amplification of all or part of the sequence of the BRCA1 gene." Again not surprisingly, the panel cites to In re Roslin Institute (another Judge Dyk opinion) for the principle that there must be a structural change to distinguish a product of nature from a patent-eligible derivative thereof.
The opinion also asserts that ssDNA binds to DNA in vitro as it does in vivo to reject Myriad's argument regarding differences in function, ignoring the fact that there is little evidence that hybridization of oligonucleotides exist in vivo. In this regard, of course, the breadth of the claims regarding any pair of primers worked against the patentee, because there was no limitation to a particular pair of primers having a particular structure that could have been argued provided the "hand of man" as required by the Supreme Court's Diamond v. Chakrabarty decision (a decision the Myriad Court followed). The opinion ends this section with its harshest statement, that there "must" be a difference in structure, relying on dicta in the Supreme Court's Myriad decision that extend the Court's rationale beyond what the case actually says.
With regard to the method claims of the '441 patent, the panel eschewed analysis under the Supreme Court's Mayo v. Prometheus decision (which was the basis argued by the appellees and inevitable amicus, the American Civil Liberties Union). Rather, the opinion held these claims to be patent-ineligible for reciting an "abstract idea" under Alice v. CLS Bank and applied that Supreme Court decision's "two-step test" to make its determination. In doing so, the panel dissected the claims to a first set of paragraphs, "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 set of paragraphs, "which describe the techniques to be used in making the comparisons and correspond to the second step of Alice."
The panel opined that these first steps are bound by the Court's earlier decision in AMP v. Myriad, wherein the "comparing" step was held to be patent-ineligible because it encompassed "an abstract mental process of 'comparing' and 'analyzing' two gene sequences." From that Myriad opinion the Court cites:
[The] claim thus recites nothing more than the abstract mental steps necessary to compare two different nucleotide sequences: one looks at the first position in a first sequence; determines the nucleotide sequence at that first position; looks at the first position in a second sequence; determines the nucleotide sequence at that first position; determines if the nucleotide at the first position in the first sequence and the first position in the second sequence are the same or different, wherein the latter indicates an alteration; and repeats the process for the next position.
Applied to the claims from the '441 patent, the panel stated that:
The methods, directed to identification of alterations of the gene, require merely comparing the patient's gene with the wild-type and identifying any differences that arise. [Citing the '441 patent specification for support.] 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.
This, of course, is an argument about preemption, but rather than cite Mayo, the opinion cited for support is Gottschalk v. Benson, 409 U.S. 63, 64 (1972) -- reminiscent of the District Court in Ariosa v. Sequenom citing Parker v. Flook rather than Mayo in support of its invalidity determination under § 101 -- and avoided any discussion regarding the applicability of § 112 to this analysis.
As for the second paragraphs of these claims, the panel stated that the District Court had found that the recited steps ("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" from claim 7, and "amplifying all or part of a BRCA1 gene from said sample using a set of primers to produce amplified nucleic acids and sequencing the amplified nucleic acids" in claim 8) "set forth well-understood, routine and conventional activity engaged in by scientists at the time of Myriad's patent applications," a characterization the Court said Myriad did not dispute. In addition, the panel stated that "the claims contain no otherwise new process for designing or using probes, primers, or arrays beyond the use of BRCA1 and BRCA2 sequences in those processes," which Myriad also did not dispute. Thus, the opinion concluded that "[n]othing 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."
Except, of course, that it was not "routine, conventional and well-understood" to use these methods to identify cancer propensity-associated mutations in human DNA, because neither the genes nor the mutations were known. The Court expressly chose not to credit that portion of the Supreme Court's opinion that seems the most related to the question before this panel:
Similarly, this case does not involve patents on new applications of knowledge about the BRCA1 and BRCA2 genes. Judge Bryson aptly noted that, "[a]s the first party with knowledge of the [BRCA1 and BRCA2] sequences, Myriad was in an excellent position to claim applications of that knowledge. Many of its unchallenged claims are limited to such applications," citing Judge Bryson's opinion concurring-in-part and dissenting-in-part with the Federal Circuit's Myriad decision (689 F. 3d, at 1349).
The opinion makes this rhetorical pirouette by focusing on the argument that the method claims at issue are similar to claim 21 of the '441 patent, which recites:
A method for detecting a germline alteration in a BRCA1 gene, said alteration selected from the group consisting of the alterations set forth in Tables 11 and 12 which comprises analyzing a sequence of the BRCA1 gene or BRCA1 RNA from a human sample or analyzing the sequence of BRCA1 cDNA made from mRNA from said sample[,] wherein a germline alteration is detected by hybridizing a BRCA1 gene probe which specifically hybridizes to an allele of one of said alterations to RNA isolated from said human sample and detecting the presence of a hybridization product, wherein the presence of said product indicates the presence of said allele in the sample.
This claim was, according to the opinion, "cited with approval" by Judge Bryson and "seemingly" also by the Supreme Court. Regardless, the opinion correctly noted that this claim was not before the Court in Myriad (Federal Circuit or Supreme Court) and thus there is no precedent regarding its validity. However, how the opinion distinguishes the patent eligibility vel non of claim 21 suggests that, once again, there is an overbreadth issue here better addressed under § 112 rather than § 101, and that if the claims at issue were so limited (i.e., to specific mutations) at least the preemption concerns would be diminished, perhaps to the point that the panel could have seen its way clear to a more favorable patent-eligibility decision.
Unfortunately, the opinion doesn't even give lip service to the direction in the Alice opinion that the claims must also be considered as a whole, using its fragmented analysis as the only justification for coming to the conclusion that the claims are not patent eligible. In doing so, the Court was able to avoid the issue of whether the claims are eligible because of the application of an old method to a new composition, which has always been patent eligible regardless of the patentability of the composition per se (and consistent with the distinctions drawn by the Supreme Court in its Myriad decision).
Finally, nowhere in the opinion does the court address the presumption of validity; this opinion suggests that, at least for patent eligibility there is no presumption (a position consistent with Judge Mayer's concurrence in I/P Engine, Inc. v. AOL Inc. (Fed. Cir. 2014)).
And to add insult to injury, the Court awarded costs to appellee.
The most grave risk arising from this opinion is that the Patent Office, which only on Monday issued revised guidelines that acknowledged that functional differences between a patented invention and a natural product can be sufficient for patent eligibility, could once again be swayed by the winds of perceived judicial fiat to renege on this more reasoned approach and return to the much-lamented structural requirement approach set out in the Guidance promulgated on March 4th. This risk is more than just a possibility, in view of the express note in the Guidance that it was a "work-in-progress" subject to further revision in view of pending Federal Circuit cases including Myriad v. Ambry. With luck, cooler heads will prevail and this decision will be limited to its facts. But in the continuing saga of the Myriad patents nothing can be considered certain, and the Office's present to the patent community of the revised Guidance could just as quickly turn to a lump of coal in our stockings.
In re BRCA1- and BRCA2-based Hereditary Cancer Test Patent Litigation (Fed. Cir. 2014)
Panel: Chief Judge Prost and Circuit Judges Clevenger and Dyk
Opinion by Circuit Judge Dyk