Yesterday, the ACLU and Public Patent Foundation scored a victory in their lawsuit challenging the validity of certain gene patents relating to genetic testing for susceptibility to breast cancer, with a district court judge deciding on summary judgment that product claims reciting isolated polynucleotides comprising naturally occurring genetic sequences, and process claims reciting methods of testing for genetic mutations, are patent ineligible under Section 101 of the patent statute. (The decision is here, courtesy of Public Patent Foundation) The court declined to address the constitutional issues raised by the plaintiffs in the case. This is an important case for biotechnology, discussed in an earlier post, but the implications are hard to assess until the Federal Circuit reviews the case on appeal.
Although the lawsuit was brought to address perceived impediments to innovation and access to genetic diagnostic testing, the decision could potentially implicate the validity of a host of other biotechnology patents, including patents used to protect biologic drugs. The scope of the decision is hard to assess; it could be interpreted as invalidating a host of issued patents claims relating to genetic inventions. Hopefully the Federal Circuit will intervene, and either reverse the decision, or at least limit its reach. But for the time being, it opens a fairly wide door for challenges to biotechnology patents based on allegations of patent ineligibility.
Some of the invalidated patent claims are directed towards isolated polynucleotides encoding BRCA proteins. The court cited to a number of relatively old judicial decisions, all pre-dating Diamond v. Chakrabarty and the Federal Circuit, which held that, at least in some circumstances, the mere isolation of a naturally occurring product does not render it patentable. Although the patent office, the courts and most of the biotechnology community have assumed for years that isolation of a polynucleotide from its native environment renders it patentable, to my knowledge there is no case directly on point to support that position.
Affymetrix, for one, has for years argued that the isolation of naturally occurring DNA does not render it patent eligible. Affymetrix sells DNA hybridization arrays, under the trade name gene chips, and not surprisingly a company whose products can include many thousands of DNA sequences representing naturally occurring genes would prefer the sequences to be unpatentable. The company filed an amicus brief several years ago in In re Fisher (a Federal Circuit case that found EST sequences unpatentable for lack of utility) arguing that isolated naturally occurring DNA sequences are patent ineligible, based in large part on the same rationale and caselaw relied upon by the court in the ACLU lawsuit.
There have been a number of cases upholding the validity of patents claiming isolated naturally occurring molecules, but the issue in those cases has been the novelty and/or nonobviousness of the molecule, not patent eligibility per se, which is a distinct doctrine. The Supreme Court's decision in Diamond v. Chakrabarty in 1980, which upheld the patent eligibility of a recombinantly modified microorganism, arguably supports the patent eligibility of isolated DNA sequences, but the district court did not read Chakrabarty so broadly.
The district court further held that even non-naturally occurring DNA molecules, such as cDNA, is patent ineligible because cDNA corresponds directly to naturally occurring mRNA, and conveys the same information as genomic DNA. The informational attributes of DNA was apparently critical to the court's decision. The court held that DNA is fundamentally different from all other biomolecules because of its primarily informational attributes, and explicitly stated that its decision did not extend to other molecules occurring naturally in the body and capable of conveying information, such as adrenaline. In other words, the decision apparently does not implicate the patent eligibility of isolated naturally occurring proteins and other biomolecules.
Even if the district court's decision were to be affirmed, the question remains as to the extent to which a DNA molecule corresponding sequence to a naturally occurring gene would have to be modified in order to render it patentable. The modification will presumably need to be sufficient such that the claimed invention has "markedly different characteristics" from the naturally occurring sequence, which is the test articulated by the court. Would a labeled probe, designed to recognize a naturally occurring mutation, be patent eligible? What about a recombinant construct comprising a DNA sequence encoding a naturally occurring protein coupled with a non-naturally occurring regulator of transcription like a promoter? How about genetically engineered cells, or chimeric sequences formed by combining two or more naturally occurring protein coding sequences? A DNA-based vaccine? The impact on biotechnology patenting could potentially be quite significant, although I predict that ultimately the Federal Circuit would not uphold the rule in a form that would so dramatically impact the ability of innovators to protect their inventions.
The district court also found that process claims reciting methods of analyzing a BRCA1 sequence for mutations, or comparing to gene sequences to see if a difference exists, are patent ineligible for failing the Bilski machine-or-transformation test. Myriad argued that the claims implicitly included physically transformative steps of isolating and sequencing DNA, but I think the court correctly rejected these arguments because no such limitation appears in the claims. One could compare two gene sequences without physically isolating or sequencing DNA, for example, if the DNA had already been sequenced by someone else and the reported sequence was being analyzed.
Essentially, Myriad obtained very broad method claims from the patent office, unlimited by any physical analysis step, but this very breadth resulted in their patent in eligibility, even though Myriad unsuccessfully argued for a narrower interpretation of its claims in order to preserve their validity.
Whether or not this is the right outcome, I think it is consistent with current Federal Circuit case law, particularly Prometheus and Bilski, although perhaps this will change after the Supreme Court decides Bilski. In Prometheus, the Federal Circuit stated that the “mental step" of observing a level of drug metabolites indicating a need to adjust the amount of drug subsequently administered is patent ineligible, which I think implies that a claim that would be infringed by merely "comparing” two DNA sequences would likewise be patent ineligible.
Interestingly, the district court went further and posited that even if the claims had specifically recited isolation and sequencing of DNA, these physical steps "would constitute no more than data-gathering steps that are not central to the purpose of the claim process,” and thus would have been insufficient to provide the necessary transformation to render the claims patentable. This is only dicta, because the challenged claims do not include this limitation, but I think the district court is clearly wrong on this one. In Prometheus, the Federal Circuit held that the physical transformation involved in performing analytical procedures to determine the level of drug metabolite in a patient was sufficient to confer patent eligibility, and I don't see how the physical transformation involved in analyzing DNA should be treated any differently.
The district court also found a claim directed to a process for cell-based drug screening, involving using a recombinant cell engineered to express BRCA1 to screen for potential cancer therapeutics, to be patent ineligible. The district court's explanation for this decision was particularly unconvincing. For example, the judge states that the claimed process is "in fact, the scientific method itself, and Claim 20 seeks to patent a basic scientific principle: that a slower rate of cell growth in the presence of a compound indicates that the compound may be a cancer therapeutics.” But the claim is limited to the use of cells recombinantly engineered to express BRCA1, and does not purport to preclude others from using the "scientific method,” or from screening for cancer therapeutics in general. I think the Federal Circuit will have to reverse this decision, because if in fact a method of screening for cancer therapeutics using a recombinantly engineered cell is patent ineligible, the implication might well be that a large percentage of patent claims relating to biotechnology are invalid.
Although clearly the ACLU/Public Patent Foundation lawsuit was motivated by a concern that gene patents impede innovation and impair access to genetic diagnostic testing, ancillary effects might extend to other aspects of biotechnology, including biopharma. In my study on human gene patent litigation, available here, I showed that gene patents have most often been used by biologic innovators to block market access by competitors, functioning as the biotechnology analog of drug patents. Although gene patents have often been the subject of criticism, very few people would argue that gene patents are unjustified when used to protect biologic drugs, thereby providing the necessary incentive for investment in the expensive and risky development of biologics.
Gene patents have played a critical role in providing intellectual property protection for biologic drugs, in part because adequate patent protection for the biologic drug itself has often not been available. For example, the first human gene patent litigation I was able to identify was Amgen v. Chugai, in which Amgen successfully asserted its patent on the erythropoietin gene to block market entry by a competing recombinant erythropoietin product (U.S. Patent No. 4,703,008). The primary claim found to be valid and infringed by the Amgen court was Claim 2, which recites: “A purified and isolated DNA sequence consisting essentially of a DNA sequence encoding human erythropoietin.” Under the district court's ruling in the ACLU case, this claim would clearly be invalid, and thus unavailable to protect Amgen's recombinant erythropoietin drug product, which has been one of the most successful biotechnology drugs and widely acknowledged as a groundbreaking tour de force of applied science.
Of course, there are other types of gene patent claims that might have been available to Amgen to block competition in the market for recombinant erythropoietin. In Amgen v. Chugai, for example, two other patent claims, claims 4 and 6, were also found to be valid and infringed.
Claim 4 recites: “A procaryotic or eucaryotic host cell transformed or transfected with a DNA sequence [consisting essentially of a DNA sequence encoding human erythropoietin] in a manner allowing the host cell to express erythropoietin.”
Claim 6 recites: A procaryotic or eucaryotic host cell stably transformed or transfected with a DNA vector [consisting essentially of a DNA sequence encoding human erythropoietin].”
The question would be whether or not the introduction of the patent ineligible erythropoietin-encoding DNA sequence into a host cell would be sufficient to render the resulting recombinant host cell patent eligible. The question is important, because without the availability of these sorts of patent claims Amgen might have been severely hobbled in its ability to achieve the patent protection warranted by its groundbreaking research. But when I read the district court's decision in the ACLU lawsuit, it seems to suggest that even these claims would be unpatentable.
For example, the decision states that even a synthetic DNA molecule (such as cDNA) is patent ineligible unless it has “markedly different characteristics” from its native counterpart. Similarly, the court found a claim reciting a method of using recombinant cells engineered to include the BRCA1 gene to screen for drug candidates was patent ineligible. If the method is patent ineligible, then one might infer that the recombinant cell itself is patent ineligible, in which case Amgen’s claims 4 and 6 would likely also be invalid.
In previous posts, I have argued that a 12 year data exclusivity period for biologics is warranted, in part because of the uncertainty of whether adequate protection is available for biologic drugs. Even with the passage of the healthcare reform legislation, which includes 12 years of data exclusivity, the issue is far from moot: the generic drug industry is already actively lobbying for new legislation to shorten the period of data exclusivity for biologics. Yesterday's decision illustrates my point, at the very least raising serious questions with respect to the availability of adequate patent protection for biologic drugs, and potentially invalidating many of the patents that biotechnology companies have relied upon to justify their investment in innovation.