By Kevin E. Noonan --
The Supreme Court rendered its opinion in Association for Molecular Pathology v. Myriad Genetics, Inc. ("the Myriad case"), and in many ways it was anticlimactic: the Court adopted the Department of Justice's position (thankfully, sans "magic microscope") by deciding that cDNA was patent eligible but genomic DNA (and fragments thereof including oligonucleotides) was not. While the biotechnology industry avoided a categorical ban on patenting DNA (which was the goal of the ACLU) or, worse, on "products of nature" no matter how altered, the Court's carefully focused opinion contains enough worrisome dicta to permit plaintiffs to declare victory even though the Court expressly disclaimed any decision on genetic diagnostic methods (which, after all, was the purported basis for the litigation in the first place).
The claims at issue are the following (remembering that claims, not inventions, are the basis for determining compliance with the patent statute):
1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.
5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.
6. An isolated DNA having at least 15 nucleotides of the DNA of claim 2.
7. An isolated DNA selected from the
group consisting of:
(a) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having T at nucleotide position 4056;
(b) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having an extra C at nucleotide position 5385;
(c) a DNA having the nucleotide sequence set forth in SEQ ID NO: 1 having G at nucleotide position 5443; and, (d) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having 11 base pairs at nucleotide positions 189-199 deleted.
U.S. Patent No. 5,747,282;
1. An isolated DNA molecule coding for a BRCA2 polypeptide, said DNA molecule comprising a nucleic acid sequence encoding the amino acid sequence set forth in SEQ ID NO:2.
6. An isolated DNA molecule coding for a mutated form of the BRCA2 polypeptide set forth in SEQ ID NO:2, wherein said mutated form of the BRCA2 polypeptide is associated with susceptibility to cancer.
7. The isolated DNA molecule of claim 6, wherein the DNA molecule comprises a mutated nucleotide sequence set forth in SEQ ID NO:1.
U.S. Patent No. 5,837,492 (recombinant vector and transformed recombinant cell claims are not named);
1. An isolated DNA comprising an altered BRCA1 DNA having at least one of the alterations set forth in Tables 12A, 14, 18 or 19 with the proviso that the alteration is not a deletion of four nucleotides corresponding to base numbers 4184-4187 in SEQ. ID. NO:1.
U.S. Patent No. 5,693,473 (nucleic acid probe claims are not recited in the complaint).
The Court's unanimous opinion by Justice Thomas, with a concurring opinion by Justice Scalia, began with a recitation of the "facts" as established below; while important this portion of the opinion raises as many issues as it purports to resolve and will be addressed below. More important to the issue before the Court (and the answer to the Question Presented, "Are human genes patentable?") is the legal rationale Justice Thomas sets forth based on these facts. The Court in a footnote also puts the standing issue to bed, stating that the only plaintiff found by the Federal Circuit to have standing, Dr. Harry Ostrer, "has alleged sufficient facts 'under all the circumstances, [to] show that there is a substantial controversy, between parties having adverse legal interests, of sufficient immediacy and reality to warrant the issuance of a declaratory judgment'" under the Court's MedImmune v. Genentech decision.
The opinion begins in the canonical way, reciting the Constitutional basis of the patent grant, Congress' decision to define patent eligibility broadly, and the Court's imposition of limitations on this breadth (wherein laws of nature, natural phenomena and abstract ideas are excluded). The opinion then provides the rationale for these exceptions, relying heavily on its recent opinion in Mayo v. Prometheus. These include that such "basic tools of scientific and technological work" should "lie beyond the domain of patent protection" because if they did not, "there would be considerable danger that the grant of patents would 'tie up' the use of such tools and thereby 'inhibit future innovation premised upon them.'" In so basing its decision on this principle in this case, the Court ignores the extensive evidence that, with regard to the BRCA genes and Myriad's patents, there has not been such a tying up of isolated BRCA DNA (including evidence of more than 10,000 scientific research reports in peer-reviewed journals regarding research on BRCA). The Court's apprehension of a "tying up" problem does not exist in this case, regardless of whether it is ever a realistic deleterious outcome of patenting.
The Court is careful to ensure that its decision is not interpreted as being a categorical ban on "naturally occurring things," reminding us that "all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas," and "too broad an interpretation of this exclusionary principle could eviscerate patent law," a concept also taken from its Mayo decision. The decision solidifies the Court's precept that patenting must achieve a "balance" between too little patenting or too much patenting, either of which the Court believes can harm innovation and thus not "promote the Progress . . . of the useful Arts."
Turning to Myriad's claims, the Court terms its Diamond v. Chakrabarty decision as being "central" to the inquiry of whether claims to isolated DNA are patent-eligible. Comparing Myriad's claims to this standard the Court opines that "Myriad did not create anything" (the limitations of this statement are discussed below). The Court then announces that "[g]roundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry"; the only saving grace in this statement is the qualifier "by itself," which prevents the sentence from being interpreted to mean that "[g]roundbreaking, innovative, or even brilliant discovery" per se would categorically be outside the scope of patenting (an interpretation that, inter alia, would be contrary to the express language of the statute). Support for this statement is, not surprisingly, Funk Bros. Seed Co. v. Kalo Inoculant Co., which the opinion describes as a case involving claims to a "mixture of naturally occurring strains of bacteria that helped leguminous plants take nitrogen from the air and fix it in the soil." The basis for the Court's decision that these claims were unpatentable is that "the composition was not patent eligible because the patent holder did not alter the bacteria in any way," and the Court analogizes the "discovery" that certain bacteria could be combined with Myriad's "discovery" of the "location of the BRCA1 and BRCA2 genes in the chromosomes." This analysis ignores several distinctions between these inventions, including (as set forth in the opinion) that the existence of the bacteria in Funk Bros. was known, and that the bacteria had been isolated and used by farmers to "inoculate" their crops to improve the level of nitrogen fixation in the soil. In the words of the Court's Mayo decision, the bacteria were "well-known, established and conventional," in contrast with the BRCA genes isolated by Myriad into a composition of matter "having a distinctive name, character [and] use."
Part of the problem, however, is the specification of the '282 patent and the way it can be (and has been) misinterpreted; the Court calls out portions of the specification that it reads as being an assertion by Myriad that its invention was the identification of the location of the BRCA genes and the association of mutations with increased breast cancer risk. The Court interprets this disclosure as "simply detail[ing] the 'iterative process' of discovery by which Myriad narrowed the possible locations for the gene sequences that it sought," and then ascribes to Myriad an attempt to "import these extensive research efforts into the §101 patent-eligibility inquiry" (finding these efforts to be unavailing). The Court also does not credit isolation of the BRCA genes as being anything more than cleaving chemical bonds of the BRCA gene from the other portions of the chromosome. In a portion of the opinion that seemingly fails to recognize how the chemical compound that is an isolated DNA molecule is claimed in English words, the opinion states that "Myriad's claims are simply not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA. Instead, the claims understandably focus on the genetic information encoded in the BRCA1 and BRCA2 genes." It is unlikely that the Court is implying that the claim should have used chemical structures to identify the isolated DNA or that such a representation would have satisfied the 101 inquiry. But by the plain meaning of the language in this sentence of the opinion, the Court ignores the well-recognized convention that a claim to "an isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2" is understood to be a representation of the chemical composition that depends on the chemical changes that differentiate the isolated DNA from the DNA as it exists in the chromosome. The opinion also prompts the conclusion that the ACLU's position that "DNA is information" was successful, despite the fact that DNA sequence information is not patented. This conclusion is reinforced by the next sentence in the opinion, that:
If the patents depended upon the creation of a unique molecule, then a would-be infringer could arguably avoid at least Myriad's patent claims on entire genes (such as claims 1 and 2 of the '282 patent) by isolating a DNA sequence that included both the BRCA1 or BRCA2 gene and one additional nucleotide pair. Such a molecule would not be chemically identical to the molecule "invented" by Myriad. But Myriad obviously would resist that outcome because its claim is concerned primarily with the information contained in the genetic sequence, not with the specific chemical composition of a particular molecule.
The Justices have passed through the looking glass to have come to these conclusions based on the evidence presented by Myriad and its amici.
The Court dealt easily and summarily with the policy question of whether calling into question thousands of patents granted by the U.S. Patent and Trademark Office would deny the Executive the deference it deserves as a co-equal branch of the Federal government. While this is not surprising from a Court where one Justice believes the PTO is "patent-happy," the position taken by the Obama administration's Justice Department "weigh[ed] against deferring to the PTO's determination" that isolated DNA claims encompassing genomic DNA were eligible for patenting. Insofar as reliance interests are relevant, the Court directs Myriad to Congress in a footnote.
The Court came to the same conclusion of patent-ineligibility for claims to oligonucleotides, despite their synthetic nature and based on the identity of the sequence of these (albeit single-stranded) molecules with the corresponding sequence in chromosomal DNA. On the other hand, the Court found that claims to cDNA "do not present the same obstacles to patentability as naturally occurring, isolated DNA segments," based on the "creation" by man of a "non-naturally occurring" DNA molecule. The Court rejected the sequence-based objections argued by Petitioners, stating that while "[t]he nucleotide sequence of cDNA is dictated by nature, not by the lab technician," "the lab technician unquestionably creates something new when cDNA is made." The only exception would be for "very short series (sic) of DNA [having] no intervening introns to remove when creating cDNA" which "may be indistinguishable from natural DNA." In another footnote, the Court rejects the argument that the existence of pseudogenes (reverse transcription copies of genes reintroduced into human chromosomes) requires cDNA to be treated as a natural product like genomic DNA, saying that "[t]he possibility that an unusual and rare phenomenon might randomly create a molecule similar to one created synthetically through human ingenuity does not render a composition of matter nonpatentable" (emphasis in opinion).
The Court in its recent patent decisions has been careful to craft them to the issue at hand and to avoid broad, precedential decisions that could implicate future technology in unpredictable ways. Justice Thomas's opinion does that here, in the final section of the opinion:
First, there are no method claims before this Court. Had Myriad created an innovative method of manipulating genes while searching for the BRCA1 and BRCA2 genes, it could possibly have sought a method patent.
[Second], 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."
Nor do we consider the patentability of DNA in which the order of the naturally occurring nucleotides has been altered. Scientific alteration of the genetic code presents a different inquiry, and we express no opinion about the application of §101 to such endeavors.
And the Court set forth succinctly its only holding:
We merely hold that genes and the information they encode are not patent eligible under §101 simply because they have been isolated from the surrounding genetic material.
There are some troubling aspects to the decision, not the least of which is the failure of the Court to recognize what in fact was claimed. The Court's opinion begins with the assertion that Myriad "discovered the precise location and sequence of two human genes, mutations of which can substantially increase the risks of breast and ovarian cancer. Myriad obtained a number of patents based upon its discovery." The Court also opines that:
It is undisputed that Myriad did not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes. The location and order of the nucleotides existed in nature before Myriad found them. Nor did Myriad create or alter the genetic structure of DNA. Instead, Myriad's principal contribution was uncovering the precise location and genetic sequence of the BRCA1 and BRCA2 genes within chromosomes 17 and 13. The question is whether this renders the genes patentable.
Of course, that is not how the claims at issue read nor how those claims would be construed in an infringement action. This failure is significant because it influences the Court's appreciation of the scope of Myriad's claims and their preclusive effects. Indeed, the information disclosed by Myriad, including the chromosomal location of the BRCA genes, their genetic sequence, and the residues that when mutated enable an increased risk of developing breast and ovarian cancer do not fall within the scope of the claims and using this information does not infringe the composition of matter claims at issue. Accordingly, the Court from the outset approaches the question of whether these claims do not promote the progress of the useful arts from a false premise, which colors and distorts the remainder of the decision.
The Court also goes astray in stating that "isolation is necessary to conduct genetic testing" when discussing the preclusive effect vel non of Myriad's isolated DNA claims. Petitioners labored mightily to conflate the effects of the genetic diagnostic method claims they challenged and the isolated DNA claims, and they were clearly successful in convincing the Court that these claims could be asserted against competitors practicing Myriad's claimed methods. That was not the case when the patents were filed and was even less the case after Myriad disclosed the positions of the diagnostic mutations in its patent specification. Once these positions were known, isolation was no longer necessary.
It is important to recognize what this opinion does not do: it does not establish a categorical "product of nature" preclusion and thus should not be interpreted as mandating that other products of nature (such as those identified by Judge Moore in her concurring opinion) are categorically unpatentable. Those cases are to come (and those inventions will be the subject of future posts). Despite the glaring scientific and technological weaknesses of the Court's opinion, it does not (fortunately) invalidate thousands of existing patents or sufficiently upset the "settled expectations" of the biotechnology community. But the opinion is another data point on a trend of the Court imposing its opinion of what is patent eligible on grounds that come perilously close to "we know it when we see it," a standard that works even less well for patenting than it did a generation ago for pornography.
Finally, Justice Scalia's concurrence is remarkable for its intellectual humility and honesty; the Justice refuses to join the portions of the opinion "going into fine details of molecular biology," the Justice stating that he is "unable to affirm those details on my own knowledge or even my own belief." Would that the remainder of the Court had come to this realization.