Pigs Fly: Federal Court Invalidates Myriad’s Patent Claims
Late on the afternoon of Monday, March 29, 2010, Judge Robert W. Sweet of the United States District Court for the Southern District of New York issued a jaw-dropping summary judgment ruling (pdf) in Association for Molecular Pathology v. USPTO that invalidates certain of Myriad Genetics’ patents related to the BRCA 1 and 2 breast and ovarian cancer susceptibility genes. In a post written immediately after the release of the opinion, Dan gave a thorough summary of the ruling. Our objective here is to offer a bit more depth on what the ruling means—and what it doesn’t mean. On the one hand, Judge Sweet’s order is radical and astonishing in its sweep. On the other, it will be some time before we have any idea what impact it will ultimately have.
We should first disclose that one of us (John) has a dog in this fight, albeit a small one. In 2003, (along with biologist and patent lawyer Roberte Makowski), John published an article in the Journal of the Patent and Trademark Office Society entitled Back to the Future: Rethinking the Product of Nature Doctrine as a Barrier to Biotechnology Patents (pdf). In that article, Roberte and John laid out an argument for challenging Myriad-style patents on “isolated” genes as claiming products that are only trivially different from the naturally-occurring versions. Judge Sweet cited this article and, in several parts of his opinion, followed the roadmap it created. So, if you oppose the Myriad patents, you’re welcome; if you like them, we’re sorry.
What Summary Judgment Means. As Dan noted, and John first wrote last fall, it is rare for plaintiffs to win on summary judgment. For either side to receive summary judgment, it must show that there are no disputed issues of fact that require a trial to resolve, and that, on the undisputed facts, the law mandates judgment in its favor. This standard is especially hard for a plaintiff to meet, since it bears the burden of proof at trial. At the summary judgment stage, a defendant can usually create an issue of fact and thereby avoid summary judgment just by saying “they have the burden of proof at trial, and a jury might not believe them.” Although this is an unusual case in that the basic facts—most notably Myriad’s patent claims and the fundamental biology and genetics that makes possible those claims—really are not in dispute, a summary judgment ruling for the plaintiffs nonetheless sends a clear message about how strong this particular judge thought their case was—and how weak he thought Myriad’s was.
The Road to Invalidation. The court broke Myriad’s patent claims into two major groups: (i) those claiming isolated DNA sequences and (ii) those claiming methods for comparing or analyzing gene sequences to identify the presence of mutations corresponding to a predisposition to breast or ovarian cancer (p. 2). Both sets of patents were rejected under Section 101 of the Patent Act, which enumerates the permissible categories of patentable subject matter: processes, machines, manufactures, and compositions of matter. As the judge noted, a long history of cases forbids claims on laws of nature, abstract ideas, and natural phenomena, which include products of nature.
Biotech Patents under Attack from Two More Angles
Two developments this month have underscored the breadth of dissatisfaction with the current state of biotechnology patenting, even as the court weighs a summary judgment motion in the pending ACLU-sponsored litigation against Myriad Genetics’ breast cancer gene patents. First, on October 2, 2009, the American Medical Association and four other medical organizations interested in genetic medicine filed an amicus brief in Bilski v. Kappos, which is now before the Supreme Court. In a decision in Bilski late last year, the Federal Circuit rejected a patent on a method of hedging in a commodities market because it was a nontransformative process consisting solely of mental steps. The Federal Circuit promulgated what has come to be known as the machine-or-transformation test, which limits patentable subject matter to processes that are either tied to a particular machine or transform the state of matter. The test has been attacked by various biotechnology and pharmaceutical interests because of its perceived limiting effect on patenting diagnostic techniques and tests.
NCI’s New BRCA1 Test: Broader Utility and Another Challenge to Traditional Genetic Tests
Contributed by Allison Williams Dobson of the Center for Genomics and Society at the University of North Carolina at Chapel Hill.
As reported last week by GenomeWeb, on September 21, 2009, a team led by Shyam Sharan from the National Cancer Institute (NCI) published the development of a new BRCA1 test based on mouse embryonic stem cells. Potentially, the test could prove useful for a much broader range of patients than the controversial Myriad Genetics BRCA1 tests.
The NCI approach focuses more on protein production than DNA analysis. The BRCA1 gene serves as the blueprint for an important tumor suppressor protein. If BRCA1 protein is not produced in sufficient quality and/or quantity, a propensity to develop cancer in the breast tissue often results. The traditional genetic testing approach asks whether a subject carries any of the BRCA1 gene variants that have been associated with increased risk for breast cancer in studies of afflicted families. NCI’s approach asks a significantly different question—rather than focusing on an identified set of “bad” gene variants, NCI asks whether a subject carries BRCA1 variants that serve as adequate blueprints for a functional protein, whether those variants have been previously identified or not. It does this by testing the protein product of the gene.
Until now, women with a family history of breast cancer have been most likely to seek a BRCA genetic test and represent the principal source of BRCA genetic data. Thus Myriad’s patented tests are based on a set of culprit BRCA gene variants found by studying primarily families with a strong propensity toward breast cancer, despite the fact that only 5-7 % of breast cancers are familial. As a result, the Myriad tests only offer useful information about a subset of BRCA1 variants. But many people (both with and without family history) carry other BRCA1 variants of unknown significance (VUS). There just are not enough empirical data yet to support conclusions about the risk associated with VUS.
ACLU Moves for Summary Judgment in Myriad Patent Case
In prior posts we’ve described the ACLU’s lawsuit challenging Myriad Genetic’s patents on BRCA1 and 2, the breast cancer susceptibility genes, and responded to readers’ questions about the effect of those patents on research. In the latest development in the case, the ACLU has filed a motion for summary judgment (the motion was filed on August 26, 2009, and the ACLU’s supporting brief can be found here (pdf).)
Summary judgment, as the term suggests, is a device whereby the judge decides the case before it ever gets to trial. The party asking for summary judgment must persuade the court that the facts are undisputed and the controlling law is unambiguous, so there is no need for a trial. As the standard is sometimes stated, it is clear at the time of the motion that no reasonable jury could find for the other side. Summary judgment, while fairly rare, is most often granted after extensive discovery (sworn deposition testimony and document production), when the parties can make an accurate forecast of what evidence would come out at trial.
Duke Finds a Second Alzheimer’s Gene—What Does It Mean?
The recent discovery of a gene linked to Alzheimer’s disease provides a timely context for revisiting the significance of gene patents. Researchers at Duke University Medical Center recently announced that they have identified a second gene (called TOMM40) associated with an increased risk of late-onset Alzheimer’s, which affects people over the age of 65. A team of Duke gene hunters originally identified the first Alzheimer’s gene (APOE) in 1993. Although the announcement prompted warnings about the need for further confirmation, the Duke researchers hope that the analysis of which versions, or alleles, of the two genes that people carry will significantly sharpen geneticists’ ability to predict susceptibility to Alzheimer’s. Those predictions might prove especially useful in both diagnosing Alzheimer’s disease and in developing future Alzheimer’s drugs.
One of the first questions on everyone’s mind, particularly in light of the high-profile lawsuit by the ACLU and others against Myriad Genetics, is whether this newly discovered Alzheimer’s gene could be patented. In principle, yes. Going back at least to the early 1980s, the U.S. Patent and Trademark Office (US PTO) and the federal courts have repeatedly taken the position that genes in isolation from their natural environment (that is, outside the body) are patentable subject matter, just like any other chemical compound. Individual cases have turned on such specifics as whether others had previously identified the gene, or whether and when the patent applicant or others had first disclosed the gene. But there is no general prohibition against patenting genes.
Whole-Genome Sequencing and Gene Patents Coexist (For Now)
In a recent post, John Conley analyzed the ACLU’s lawsuit challenging Myriad Genetics’ patents on the BRCA-1 and BRCA-2 “breast and ovarian cancer susceptibility” genes. Several readers responded with the same general inquiry: if an individual undergoes a whole-genome sequence analysis, will the individual (or the company providing the sequence) be required to pay royalties to Myriad because the BRCA-1 and -2 loci will have been sequenced?
Although focused on the BRCA genes, the question is broadly applicable to the entire genome sequencing industry: when sequencing all or a portion (e.g., the exome) of an individual’s genome, are individual gene patents infringed upon by either the company providing the sequence or the individual purchasing or requesting it? The answer is not entirely clear, but, at least in the case of Myriad and the BRCA genes, it appears to be no. Or at least, not yet.
Let’s begin with what is not patented, which includes a majority of genes and the vast majority of the human genome. Genes—those stretches of DNA that encode for proteins—make up approximately 2% of the human genome. The estimate of the exact number of genes ranges from between roughly 20,000 to 30,000 and, of those, a 2005 study in the journal Science found that only 20% of human gene DNA sequences are patented (subscription). Although those numbers are certainly subject to change, the reality is that, today, it is likely that less than 1% of the entire human genome has been patented.
Of course, that very small number belies the fact that the genes which have been patented consist of some of the most important identified genes associated with the prediction or determination of human health and disease. The high-profile BRCA genes are an excellent example and thus make for a good case study.
ACLU v. Myriad Genetics: Defendants Move to Dismiss
The US Patent and Trademark Office, the University of Utah and Myriad Genetics have all filed motions seeking to dismiss the ACLU’s high-profile lawsuit attacking the patentability of genes (pdfs: USPTO Memorandum; Myriad/Utah Memorandum). In alleging that the plaintiffs lack standing to bring the lawsuit — a common procedural tactic in litigation — Myriad does not mince words, opening its argument as follows:
This case is a thinly veiled attempt to challenge the validity of patents where, other than an overall policy disagreement concerning the legitimacy of gene patents, the plaintiffs have no actual dispute with the Defendants over patent infringement. If the plaintiffs in this case have standing, then virtually anyone can challenge any patent at any time.
The ACLU has yet to publicly comment on the motions to dismiss. The court is scheduled to hear the Motion to Dismiss (pdf) on August 26th.
The ACLU v. Myriad Genetics Suit: Legitimate Challenge or Publicity Stunt?
By now everyone has heard of the ACLU-instigated suit against Myriad’s patents on the breast cancer susceptibility genes BRCA1 and BRCA2 (read: ACLU release; the complaint). These patents emerged from research at the University of Utah and were assigned to Myriad, a private spinoff. The broadest product claims cover “an isolated DNA coding for a BRCA1 [or 2] polypeptide [protein], said polypeptide having the amino acid sequence” listed in the patent. Related patents also challenged in the suit cover methods for screening for genetic mutations. As a result of these patents, research and diagnostic testing involving BRCA1/2 must be done by or with the approval of Myriad, usually at some cost.
The ACLU has assembled a broad coalition of authoritative and sympathetic plaintiff. They include medical and scientific organizations, individual researchers and physicians, the women’s health cooperative that publishes Our Bodies, Ourselves, and cancer patients who allege that they need but cannot afford (and cannot get their insurers to pay for) BRCA1/2 testing. The defendants are Myriad, the U.S. Patent and Trademark Office, and several directors of the University of Utah Research Foundation.
The suit comes against the background of some recent decisions that nibble around the edges of gene patentability. Earlier this year, in In re Kubin, 561 F.3d 1351 (Fed. Cir. 2009), the Federal Circuit affirmed the PTO’s obviousness rejection of a patent on polynucleotides that encode natural killer cell activation proteins (the NK cells help fight infections and cancer). The holding was that it would have been obvious to try to isolate these nucleotide sequences in light of existing knowledge of the proteins in question and the sequencing methods. Back in 1995, in In re Deuel, the Federal Circuit had had rejected this “obvious to try” objection to a generally comparable gene patent. But now the same court took the view that the Deuel had been “discredited” by the Supreme Court’s 2007 obviousness decision, KSR International v. Teleflex.
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