In a thoughtful opinion of March 29, Judge Robert Sweet has adopted a position that, if widely accepted, would invalidate essentially all DNA patents. In Association for Molecular Pathology v. U.S. Patent and Trademark Office, Judge Sweet, of the Southern District of New York, cites Supreme Court precedent in support of his view that isolated genes are directed to a “product of nature” and are therefore not eligible to be patented.

In fact, the decision flouts recent holdings of the Federal Circuit and sets up a potential fight in the Supreme Court about what kinds of things can be protected by patents.

Factual Background

The surprising holding resulted from a case filed by the American Civil Liberties Union on behalf of a variety of nonprofit medical and research societies, scientists and cancer patients. The plaintiffs sued to invalidate claims related to two human genes in patents owned by Myriad Genetics and the University of Utah Research Foundation.

They argued that the patents were issued in violation of the Patent Act; the patent and copyright clause of the United States Constitution (Article I, Section 8, Clause 8); and the First and Fourteenth Amendments to the Constitution.

The fundamental question is whether purified DNA sequences and inventions utilizing such sequences are patentable. DNA is a chemical molecule composed of a very long series of four kinds of deoxyribose nucleotides, the specific sequence of which carries genetic information. DNA is transcribed into ribonucleic acid (“RNA”), which is translated into proteins. Proteins are polymers of amino acids linked together in a specific sequence, as dictated by the sequence of the DNA.

Proteins in turn are key structural and functional elements in cells, and participate in nearly all cellular activities. A gene, therefore, is a unit of heredity comprised of an entire nucleotide sequence in a complex of DNA and proteins known as chromatin that will frequently encode the production of a functional protein in an organism

The sequences at issue comprised part of the genetic sequences encoding the BRCA1 and BRCA2 proteins. Due in large part to the efforts of several of the inventors of the patents at issue, these genes are now recognized as important predictors of breast cancer. Women who inherit mutant forms of the BRCA genes have a high probability of developing breast and/or ovarian cancer before the age of 50.

The inventors identified the correlation between BRCA mutations and breast cancer. They proceeded to isolate or purify the gene from human cells–a process that involves removing the gene from a complex arrangement of DNA and chromosomal proteins–and cloned and sequenced a complementary DNA (“cDNA”) of the BRCA mRNA, thereby revealing the amino acid sequence of the BRCA proteins.

Myriad Genetics was founded by one of several scientists conducting the pioneering work on the BRCA1/2 genes. Myriad eventually received seven patents covering various aspects of purified BRCA1/2 DNA sequences, their corresponding amino acid sequences, and methods of using the DNA and amino acid sequences to test and identify cancer-predisposing mutations in patients.

Of the dozens of claims in these patents, the plaintiffs challenged fifteen as being unpatentable subject matter, including claims to isolated gene-encoding DNA itself (or fragments thereof) and method claims covering use of the isolated DNA.

The Shifting Sands of Patent Eligibility

Whether or not an invention is patent eligible depends on section 101 of the Patent Act. This seemingly simple statute defines as eligible for a patent “any new and useful process, machine, manufacture or composition of matter . . . .” The meaning of these terms, however, has evolved over years of case law interpreting the statute, which was enacted as part of the Patent Act of 1952.

Since 1952, there has been a gradual broadening of subject matter eligible for patents. The Supreme Court has held upheld patents for genetically engineered microorganisms (Diamond v. Chakrabarty, 1980) and the use of software used to control machinery (Diamond v. Diehr, 1981). In turn, the Federal Circuit has expanded patent eligibility in many areas, including, for example, computer-implemented inventions for business methods (State Street Bank & Trust Co. v. Signature Financial Group, 1998).

State Street Bank, the high-water mark of patent eligibility, cited Chakrabarty and the committee reports accompanying the Patent Act for the proposition that Congress intended the patent eligibility requirements to extend to “anything under the sun that is made by man.”

The past few years have marked a period of retrenchment in patent eligibility. The Supreme Court, in Laboratory Corp. of America Holdings v. Metabolite Laboratories, Inc. (2006), denied review to a patent for a medical diagnostic method. The court’s dismissal order generated a dissent by Justice Breyer that has become oddly influential for a case that went undecided. He expressed the view that a correlation between a specific measurement and a vitamin deficiency required by the patent in suit is a “natural phenomenon” and therefore the invention should not be eligible for a patent.

Indeed, a long line of cases have pronounced that laws of nature, scientific principles, physical phenomena, abstract ideas, physical substances unchanged from their natural state, and processes that do not alter physical substances are unpatentable categories of subject matter. As the Supreme Court stated in Gottschalk v. Benson (1972), “Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.”

Although the Benson case, holding that a computerized method for converting binary coded decimals into binary was not patent eligible, was mooted a decade later by Diamond v. Diehr, and although Justice Breyer was writing only for the minority in Laboratory Corp., both of these opinions were quoted with approval by Judge Sweet in his March 29 decision.

The Supreme Court is expected imminently to issue its decision in Bilski v. Doll,which addresses patent eligibility for business methods, both computer-implemented and otherwise. [See our discussion of the Federal Circuit’s decision.] The test for patent eligibility articulated by the Federal Circuit in Bilski has already narrowed the standard for process patents from “anything under the sun that is made by man” proclaimed in State Street Bank to a “machine or transformation” test: to be patent-eligible, a process must either transform matter or be carried out by a particular machine or apparatus.

The Federal Circuit in Bilski took time to discuss points raised by the Supreme Court dissenters in Laboratory Corp. because the Federal Circuit does not share the narrow view of patent eligibility taken by Justice Breyer and his fellow dissenters.

In a later case similar to Laboratory Corp., Prometheus Laboratories, Inc. v. Mayo Collaborative (2009), the Federal Circuit held that a diagnostic method involving the administration of a drug to a human and measuring the metabolites produced by the body constitutes a sufficient transformation to pass muster under Bilski and constitutes patent eligible subject matter.

One concern underlying decisions limiting patent eligibility is that patent rights might overspread the basic tools of science and research, and inhibit the use of those tools for further discovery and innovation. As stated by Justice Douglas of the Supreme Court in Funk Bros. Seed Co. v. Kalo Inoculant Co. (1948), “manifestations of laws of nature” are “part of the storehouse of knowledge,” “free to all men and reserved exclusively to none.”

Funk denied validity to a patent for a mixture of strains of root-nodule bacteria, which, unlike those known in the prior art, did not exert a mutually inhibitive effect on one another. Even though the Funk decision has been all but overruled byDiamond v. Chakrabarty and Diamond v. Diehr, Funk, too, was cited with approval by Judge Sweet in his March 29 decision.

Another line of cases holds that substances unchanged from their natural form are not patentable because they are products of nature. This rule, however, has long been subject to a purification exception.

In Parke-Davis v. H.K. Mulford Co. (S.D.N.Y. 1911), Judge Learned Hand held that the prohibition on patenting products of nature does not preclude patenting purified substances as long as the characteristics of the purification process rendered the substance “for every practical purpose a new thing commercially and therapeutically.” Ever since this ruling, court decisions have been nearly uniform in agreeing that DNA is patent eligible as a purified natural substance.

Judge Sweet’s View

Gene patenting, however, is a highly charged and contentious issue. Many scientists and lay people strongly oppose DNA-based patents on the grounds that they come close to patenting laws of nature. From one perspective, all that the DNA patentee has done is to identify pre-existing evolutionary design.

The worry is that a proliferation of DNA patenting has limited the openness of scientific exchange, chilled research and unfairly increased the costs of genetic tests for consumers. Nonetheless, biotechnology companies rely on these patents to justify assuming the risks and capital costs associated with commercializing an invention.

Judge Sweet’s lengthy opinion in Molecular Pathology concludes that (1) isolated DNA is of the same fundamental quality of DNA as it exists in cells and, therefore, claims directed to isolated DNA are not patent eligible subject matter under section 101; and (2) the method claims of the patents are abstract mental processes which likewise constitute unpatentable subject matter under the test articulated by the Federal Circuit in Bilski.

Judge Sweet opines that the case law on the patentability of purified, naturally-occurring chemicals, including Parke-Davis, is not as authoritative as many would believe. Several of the bedrock cases upon which the purification doctrine is based have never been enthusiastically adopted by the Federal Circuit.

On the other hand, the Federal Circuit has decided many cases involving purified and/or recombinant DNA and has never found it necessary to comment on whether or not the inventions are patent eligible under section 101. This implicit acceptance of the purification doctrine is notable given the extent to which many judges treat the question of whether the case before them involves patent eligible subject matter as a fundamental question to be addressed before all others.

Furthermore, at least three of the cases upon which Judge Sweet heavily relies (Funk; the dissent in Laboratory Corp.; and Gottschalk v. Benson, discussed above) are of questionable authority themselves, having rarely – if ever – been cited by the Federal Circuit and having had little impact on modern law. And while Molecular Pathology distinguishes several cases cited by the defense on the ground that they focused more on issues of novelty than patentable subject matter, the cases relied on by the judge and plaintiffs are guilty of the same confusion.

The judge may have philosophical objections to the temporary monopolies afforded by patents when they limit access to clinical tests and treatments. The opinion is heavily influenced by academic arguments on the potential of biotechnology patents, particularly gene patents, to retard innovation and hinder basic research. However, there is little or no empirical evidence to support these assertions.

According to a study published by the National Research Council, the number of biotech projects abandoned or delayed as a result of technological access difficulties is quite small, as is the number of reported instances where investigators have had to revise their research protocols because of intellectual property issues.

A quick search of biomedical databases, on the other hand, shows that over 6000 academic articles have been published on BRCA1 and BRCA2 over the last ten years. And likewise, Myriad’s enforcement efforts were limited to for-profit ventures and did not include purely academic endeavors.

In addressing the method claims asserted by Myriad, Judge Sweet cited the Federal Circuit’s Bilski decision and its “machine or transformation” test to evaluate the patent eligibility of the claims. In doing so, Judge Sweet spent considerable time trying to distinguish the Federal Circuit’s subsequent decision in Prometheus Laboratories, in which the Federal Circuit held a diagnostic method to be patent-eligible subject matter.

Judge Sweet reasoned that the allegedly transformative acts of Myriad — the DNA isolation and sequencing — took place prior to, rather than as a part of, the diagnostic evaluation, and as a result do not satisfy the Bilski test.

The linchpin of Judge Sweet’s opinion is its most legally and scientifically questionable assumption. He reasoned that the utility of DNA is derived entirely from the information inherent in its nucleotide sequence and that isolated DNA in that respect merely mimics the information of natural DNA.

Judge Sweet acknowledged that the isolation of DNA removes it from the complex arrangement of chromosomal proteins (i.e., chromatin) in which it is integrated in vivo. He asserted, however, that isolated DNA is not “markedly different” from natural DNA because both isolated and natural DNA share the same information content.

Judge Sweet’s view of DNA as information content stems from a failure to appreciate that isolated DNA isfunctionally and structurally different from its natural form in vivo. It is the complex of DNA and chromosomal proteins within a cell that determines whether the information content is used.

The complex three-dimensional architecture of natural DNA and proteins determines whether a gene is turned on or off and how frequently the gene is transcribed into mRNA. The structure of the DNA/protein complex is integral to its function. In other words, natural DNA would have no protein-encoding information to impart if it were to exist outside chromatin.

Looking Forward

Many judges look askance at efforts to patent what they view as phenomena of nature that the patentee has merely discovered. This is what animates Judge Sweet’s approach in Molecular Pathology, much as it did Judge Breyer’s dissent inLaboratory Corp. and Justice Douglas’s opinion for the majority in Funk.

In contrast stands Judge Giles Rich, who not only wrote the State Street Bankopinion, but also coauthored the Patent Act of 1952. In State Street Bank, Judge Rich agreed that another category of subject matter, abstract ideas, is not patent eligible even if reduced to mathematical algorithms. However, he held that the transformation of data through the use of algorithms to achieve a useful and tangible result was patent eligible.

Similarly, the question on appeal will be whether Myriad’s isolated DNA sequences are sufficiently transformative of naturally occurring DNA to constitute patent eligible subject matter. Judge Sweet has answered this question in the negative on the basis of questionable scientific and legal analysis.

The Federal Circuit’s recent decisions, including Prometheus Laboratories, suggest that it will reverse Judge Sweet, a result that Judge Sweet may have anticipated by referring more to decisions of the Supreme Court than of the Federal Circuit.

If the Federal Circuit reverses, the question then will be up to the Supreme Court. Will it review the case, and if so, will the dissenters in Laboratory Corp. (one of whom, Justice Stevens, is retiring this year) be able to persuade the majority of their view? If the Laboratory Corp. dissenters were to prevail, the unfortunate trend in the weakening of patents would continue.