BRCA 1 and BRCA 2 genes are found to be associated with the increased risk of breast cancer as well as ovarian cancer. In 1990, a team of scientists from University of California, Berkeley declared the association of BRCA 1 gene (present in long arm of chromosome 17) with the risk of breast cancer.[ii] In 1994, researchers of Myriad genetics along with colleagues at the University of Utah, the National Institutes of Health (NIH), and McGill University isolated and published the sequence of BRCA 1.[iii] In the same year, the first BRCA 1 U.S. patent was filed by the University of Utah, National Institute of Environmental Health Sciences (NIEHS), and Myriad. In 1995 isolation and sequencing of the BRCA2 gene was done by Myriad, in collaboration with University of Utah and the first BRCA2 patent was filed in the U.S. In 1996, Myriad launched their BRCA Analysis product, which detects certain mutations in the BRCA1 and BRCA2 genes that put women at high risk for breast cancer and ovarian cancer. USPTO issued several gene patents to Myriad Genetics and the University of Utah Research Foundation, allowing extensive control over BRCA1 and BRCA2 breast cancer genes. The patents also contained some broad claims to diagnostic methods. Myriad is the only laboratory in the United States where commercial diagnostic testing for BRCA1 and BRCA2 can be performed. Moreover, the tests are expensive and Myriad has charged a relatively high rate (over $3,000) for the tests, which places them out of the reach of many.
Facts
The AMP (Association for Molecular Pathology) with the University of Pennsylvania, researchers at Columbia, NYU, Emory, and Yale; and with several patient advocacy groups and several individual patients filed the case against Myriad, the Trustees of the University of Utah, and the U.S. Patent and Trademark Office (USPTO). The USPTO was severed from the case by the district court. The complaint made against specific claims on isolated genes, diagnostic methods, and methods to identify drug candidates, in seven of Myriad’s 23 patents on BRCA1 and BRCA2.[iv] The plaintiffs claimed that these patents were invalid on the grounds that they are not patentable subject matter under §101 of Title 35 of the United States Code as the isolated genes are unpatentable products of nature, and that the diagnostic method claims are mere thought processes that do not yield any real transformations, and that the drug screening claims were just describing the basic processes of science.
According to USPTO, genes are chemical compounds, though complex ones, and thus qualify for potential patenting as compositions of matter. Naturally occurring product cannot be patented, but the USPTO has allowed patents on genes, naturally occurring products, that have been purified, isolated, or otherwise altered. For this reason, gene patents have been issued in the U.S. for decades. The National Institute of Health estimates the number of patents in the United States that cover “isolated” or “purified” genes to be around 20% of all human genes. These include genes that have been associated with different forms of cancer, Alzheimer’s and other diseases.
Count of Myriad’s patent claims can be divided into two parts: (i) For isolated DNA sequences and (ii) For methods of comparing or analyzing gene sequences to identify the presence of mutations corresponding to a predisposition to breast or ovarian cancer.[v] Both sets of patents were rejected under Section 101, which enumerates the permissible categories of patentable subject matter: processes, machines, manufactures, and compositions of matter. As the judge of District Court noted, a long history of cases forbids claims on laws of nature, abstract ideas, and natural phenomena, which include products of nature.
Isolated DNA Sequences denoted as insufficiently distinct from naturally occurring genes in the body. Whether a patent application for subject matter is patentable or not, is based on novelty, utility, and non-obviousness criteria. To establish the said criteria, the court went to assess how different an “isolated” gene would have to be to avoid characterization as a product of nature. Myriad defined “isolated” in its patents as “substantially separated from other cellular components which naturally accompany a native human sequence [such as] human genome sequences and proteins”.[vi] As a reference Myriad argued on some cases going back to the early twentieth century which especially one involving purified adrenaline.[vii]
The judge disagreed strongly and went back even further, to nineteenth-century cases involving line fibers and wood pulp, as well as later cases involving such things as pure tungsten, and concluded that “purification of a product of nature, without more, cannot transform it into patentable subject matter. Rather, the purified product must possess ‘markedly different characteristics’ in order to satisfy the requirements”.[viii]
Myriad’s isolated genes failed this test. In his search for “markedly different characteristics,” Judge Sweet presumably held that critical functional property of a gene is its ability to carry the information sufficient and necessary to code for a protein, whether in the body or in isolation. DNA represents the physical embodiment of biological information, distinct in its essential characteristics from any other chemical found in nature. It is concluded that DNA’s existence in an ‘isolated’ form alters neither this fundamental quality as it exists in the body not the information it encodes. The preservation of this defining characteristic of DNA in its native and isolated forms mandates the conclusion that the challenged composition claims are directed to unpatentable products of nature.[ix]
From the very beginning of gene patenting, patent lawyers have taken the stand that genes are just chemicals. Their information carrying function is irrelevant to their patentability. Because genes are chemically different in isolation, at least in a literal sense, they can’t be considered products of nature. The USPTO and the courts, including the patent court of appeals have uniformly submitted.
Myriad’s process claims also failed to fulfill the patentable criteria. The court conducted the “machine or transformation” test for method claims (This test comes from the recent Bilski case; although the Supreme Court will soon issue its own opinion on Bilski case, the machine or transformation test is the law unless and until the Supreme Court orders otherwise). Judge Sweet found that none of the methods were coupled to any particular machine, nor did they bring about a tangible transformation of anything. As per his judgment, “because the claimed comparisons of DNA sequences are abstract processes, they also constitute unpatentable subject matter and physical transformations associated with isolating and sequencing DNA, they would still fail the ‘machine or transformation’ test under §101 for subject matter patentability”.[x]
In reference to the said case, it is relevant to maintain that in 2007, the European Patent Office (EPO) rejected an appeal by Myriad Genetics and the University of Utah, relating to the BRCA1 gene and its applications. There was widespread objection to the extent of this claim among European researchers, since it granted an effective monopoly to Myriad which they believed unjustified; six bodies filed objections, leading to a decision by the EPO in 2005 to substantially amend the patent, retaining only the claims relating to a specific nucleic acid probe and vectors containing gene sequences. The EPO has now rejected an appeal by Myriad and the University of Utah, and amended the patent, meaning that European laboratories retain the right to perform diagnostic tests for mutations in the BRCA1 gene sequence, which are associated with increased susceptibility to breast and ovarian cancer.
Myriad’s appeal at United States Court of Appeals for the Federal Circuit was granted and the case was heard in 2011. On July 29, 2011, Judge Alan Lourie of the Federal Circuit reversed the district court’s decision saying that an isolated DNA sequence and that methods for screening cancer therapeutics is patent-eligible; but agreed with the district court’s decision that Myriad’s claims for comparing DNA sequences are patent-ineligible. The reason shown is that isolated DNA is chemically distinct from the natural state of a gene in the body.[xi]
AMP, being unsatisfied with the judgment of the United States Court of Appeals for the Federal Circuit, applied for the review of the case in the Supreme Court. Supreme Court granted the review on March 26, 2012 after vacating the judgment of Federal Circuit. The reference of the recent decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc.,[xii] is cited where the Court ruled that certain kinds of claims in medical diagnostics patents, including natural phenomena, were not patentable. The Supreme Court wanted the Federal Circuit to take this precedent into account while reviewing this case. But eventually, the decision of Federal Circuit after second hearing also was almost the same as before and moreover they found that the Mayo precedent was not particularly relevant to this case, as it did not deal with the patent eligibility of gene patents.[xiii]
American Civil Liberties Union and the Public Patent Foundation filed another petition in the Supreme Court after the second Federal Circuit Decision, on September 25, 2012. On November 30, 2012, the Supreme Court had agreed to hear the plaintiffs’ appeal.[xiv] After hearing the United States Supreme Court held that an isolated segment of naturally occurring DNA segment is a product of nature and is not patent eligible, the simple reason behind that is it has been isolated from the gene and it contained the same genetic information as that of natural DNA. On the other hand the Court held that, as cDNA sequence is an exons-only molecule and is not naturally occurring, thus is eligible for patenting in the United States.
Analysis
BRCA 1 & BRCA 2 gene patents to Myriad Genetics by USPTO, allowed extensive control over BRCA1 and BRCA2 breast cancer genes by Myriad. The patents also contained some broad claims to diagnostic methods. So it becomes practically impossible for other companies to test those genes and develop alternative tests; women left with no other choice but to use only Myriad; as Myriad is the only laboratory in the United States where commercial diagnostic testing for BRCA1 and BRCA2 can be performed. The Myriad after getting exclusive rights over testing, had consistently refused to grant licenses to allow any other parties to perform testing, which marginalized the at-risk women. So the Supreme Court decision has come as a welcome move for all the at-risk women, as well as the companies engaged in the research and development regarding the BRCA 1 & BRCA 2 mutation diagnostic methods.
In the positive note, non-patentability of the isolated DNA is well appreciated because from the diagnostic perspective; research and development can get wider scope as the researchers can find out the new linkages between specific disease with the specific gene sequence responsible for the disease. Not only that, it can solve the public interest issue. The diagnosis and treatment price rise due to patent can be minimized because of more competition between different companies. Even, the triple test of patent criteria is well established by this particular decision where the word “invention” is properly defined.
On the contrary, cDNA is necessary tool for making gene probes and doing gene cloning; which are very much helpful for research and development for gene therapy. Patenting of cDNA will hinder the public health and public interest issue in general. Now the gene therapy is available only for ‘cystic fibrosis’ but in future it may prove itself to be a very effective treatment modality for various diseases including cancer. Researchers may face a roadblock as a consequence of the patentability of cDNA.
REFERENCE
[i] Case citation No. 12–398. Argued April 15, 2013—Decided June 13, 2013; available online at https://www.supremecourt.gov/opinions/12pdf/12-398_1b7d.pdf (accessed on 18.06.13)
[ii] Hall, J. et al (1990). “Linkage of early-onset familial breast cancer to chromosome 17q21”. Science 250 (4988): 1684–1689.
[iii] Miki, Y. et al (1994). “A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1”. Science 266 (5182): 66–71.
[iv] Schwartz, John and Pollack, Andrew (March 29, 2010). “Judge Invalidates Human Gene Patent”. The New York Times. Retrieved March 29, 2010.
[v] Page 2 of Case 1:09-cv-04515-RWS Document 255 Filed 03/29/2010 available online at: https://www.aclu.org/files/assets/2010-3-29-AMPvUSPTO-Opinion.pdf (accessed on 04/2/2010)
[vi] Page 92 of Case 1:09-cv-04515-RWS Document 255 Filed 03/29/2010
[vii] https://pubs.acs.org/subscribe/archive/mdd/v04/i12/html/12timeline.html
[viii] Page 121 of Case 1:09-cv-04515-RWS Document 255 Filed 03/29/2010
[ix] Page 125 of Case 1:09-cv-04515-RWS Document 255 Filed 03/29/2010
[x] Page 147 of Case 1:09-cv-04515-RWS Document 255 Filed 03/29/2010
[xi] United States Court of Appeals for the Federal Circuit Docket 2010–1406, Decided July 29, 2011. Appeals Court Decision
[xii] 566 U.S. ___ (2012); 132 S. Ct. 1289.
[xiii] Conley, John. “Applying Mayo to Myriad: Latest Decision Brings No New News”. Genomics Law Report. Retrieved October 14, 2012.
[xiv]Kevin E. Noonan for Patent Docs Blog, September 25, 2012. ‘Plaintiffs (Again) File Certiorari Petition in Myriad Case’.