Department of Justice Seeks to

Handcuff Gene Patents

 

By Justin Huddleson, Ph.D., a member of our Patent Practice Group

 

L

ast spring, in the so-called Myriad Genetics case, Judge Robert Sweet of the federal court in New York City famously invalidated nearly all DNA-based patents in a sweeping opinion that we discussed in our April 2010 issue. 

The case is now on appeal to the Federal Circuit, and the Department of Justice has filed an amicus curiae (“friend of the court”) brief on behalf of the U.S. government.  The U.S. had never before expressed its views on this question in the litigation context. 

Although the Department sought to temper Judge Sweet’s holding and find an acceptable middle ground, its brief argues that isolated genomic DNA is not patent-eligible.  However, it fails to provide a rational basis for excluding isolated genetic sequences from the realm of patentable subject matter. 

To review, the case started when the American Civil Liberties Union orchestrated a challenge on behalf of various nonprofit medical and research societies, scientists and cancer patients.  These plaintiffs sued to invalidate patent claims related to two human genes in several patents owned by Myriad Genetics and the University of Utah Research Foundation. 

The patents cover 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. 

The sequences at issue comprise part of the genetic sequences encoding the BRCA1 and BRCA2 proteins.  These genes are now recognized as important hereditary predictors of breast cancer. 

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. This revealed the amino acid sequence of the BRCA proteins.

The fundamental issue before the district court was whether isolated, purified DNA sequences and inventions utilizing such sequences are patent-eligible. 

On March 29, 2010, Judge Sweet concluded that (1) isolated DNA within the meaning of the patent is of the same essential quality of DNA as it exists in cells and, therefore, claims directed to isolated DNA are not patent-eligible subject matter; 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, and later affirmed by the Supreme Court, in In re Bilski. 

Before this case took off, the law regarding patentability of purified natural substances had been largely set in 1911 by the influential case of Parke-Davis v. H.K. Mulford Co.  There, 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, courts have been nearly unanimous that DNA is patent-eligible as a purified natural substance.  Judge Sweet’s opinion turned this well-settled understanding upside-down.

The rationale of Judge Sweet’s opinion is that DNA is a natural substance encoding the genetic inheritance of humankind and, therefore, any inventions that use this common genetic information are unpatentable because the purification or isolation does not change the genetic information of interest. 

In other words, although isolated or purified DNA does not exist in nature per se, the genetic information it encodes is no different in either degree or kind.  One problem with this reasoning is that it could be extended to exclude from patent eligibility a wide range of biotechnical inventions-- from genetic tests and biomarkers to isolated microbial strains and small molecules.

The Department of Justice seeks a middle ground amidst the concerns of patients, the academic community, and the biotech industry.  Its brief recognizes that Judge Sweet went too far.  Contrary to some assertions by the ACLU, the brief does not wholly support its arguments and does not take the position that all gene-based inventions are unpatentable.  It is worthwhile to consider what the brief actually states:

[T]he district court erroneously cast doubt on the patent-eligibility of a broad range of manmade compositions of matter whose value derives from the information-encoding capacity of DNA.  Such compositions — e.g., cDNAs, vectors, recombinant plasmids, and chimeric proteins, as well as countless industrial products, such as vaccines and genetically modified crops created with the aid of such molecules — are in every meaningful sense the fruits of human ingenuity and thus qualify as “human-made inventions” eligible for patent protection….

The brief goes on to explain that the patent laws embrace gene replacement therapies, engineered biologic drugs, methods of modifying the properties of plants and other organisms. 

Importantly, the DOJ emphasizes that cDNAs are and should continue to be patent- eligible.  cDNA is copied from a naturally occurring mRNA molecule in a laboratory.  Sequencing cDNA permits the amino acid sequence of the encoded protein to be deduced, and expression of cDNAs in recombinant cells can be used to produce large quantities of their encoded proteins in vivo. 

cDNAs are necessary in many gene-based inventions, representing a primary means by which genes are utilized in the laboratory and the marketplace, including for genetic testing.  Therefore, the Department’s recommendations would preserve the patentability of many genetic inventions. 

However, the amicus brief unequivocally supports Judge Sweet’s holding that genomic DNA that has been isolated from the human body, without further alteration or manipulation, is not patent-eligible. 

The DOJ argues that unmodified genomic DNA is a product of nature and not, therefore, a “human-made” invention.  In fact, the brief’s criterion for patent eligibility is the extent to which human intervention is needed to create the invention.   More specifically, the amount of intervention must be sufficient to transform a product of nature into a human-made invention that is different in structure and function from the natural product. 

The DOJ leaves unclear why human intervention is sufficient in some circumstances but not others.  For example, the brief emphasizes that cDNAs are patent-eligible because they consist only of the protein-encoding segments of a gene.  Genes are comprised of coding regions, exons, and non-coding regions, or introns.  However, cDNAs are made from mRNAs, and mRNA must be isolated and purified before cDNAs can be made. 

Moreover, the removal of the introns, which the brief seems to credit to human ingenuity, is actually accomplished by cellular machinery making the mRNAs.  It is routine to then isolate the mRNA and turn it into cDNA.  If the immediate precursor is patent-ineligible, what marks the spot from which human intervention is enough to justify eligibility?

The DOJ seems to argue there must be enough intervention to turn a “product of nature” into an unnatural product.  For at least three reasons, this reasoning fails to satisfy.  First, the line demarcating a natural product from an unnatural product is not necessarily clear.  Every molecule can be defined as a “product of nature” because every molecule is a consequence of natural laws governing chemical bonding, thermodynamics, intra-molecular interactions, etc. 

Moreover, long genetic sequences mimicking naturally occurring genes can now be synthesized de novo in a laboratory.  Would these artificial genes, which never existed in a cell, be patentable even though their DNA sequences and utility are identical to a product of nature?  Basing patent eligibility on such an arbitrary distinction would continue to cast doubt on a wide range of inventions using DNA, biomarkers and even small-molecule pharmaceuticals.  

Second, such reasoning runs against established law.  The Supreme Court set the standard for patent-eligible subject matter in the famous case of Diamond v. Chakrabarty (1980).  There, the court stated that “laws of nature, physical phenomena, and abstract ideas” are not patent-eligible.  As categorical examples, the court listed “a new mineral discovered in the earth or a new plant found in the wild”, E=mc², and the theory of gravity.  Products of nature are notably absent from this list.

Finally, isolated DNA does not encompass genes as they exist naturally in any cell and so do not constitute “products of nature.”  Once removed from the cellular architecture, DNA sequences cease to function as genes, differing both structurally and functionally. 

Structurally, the sequences take on different three-dimensional configurations that determine when the genetic information can be used.  Functionally, the DNA sequences are not used to express proteins for use in the cell from which they were isolated.  They are, for all purposes, a different thing from any individual’s genes. 

Reasonable minds may differ about the meaning of terms such as “isolated DNA” and “product of nature.”  This fact, above all else, may be what makes a workable doctrine for DNA- and gene-based patents so difficult. 

Ultimately, the Federal Circuit may be able to dodge the more difficult doctrinal issues by deciding the case on procedural grounds.  There are serious questions, for example, whether the plaintiffs have constitutional standing to bring a lawsuit, and the Supreme Court may be disinclined to review a case decided on that basis. 

In any event, the U.S. government has made its feelings known, in a brief that, startlingly, contradicts the policy of the Patent and Trademark Office to grant patents on human genes.  Everyone interested in the biotech industry will anxiously await the next development in the Myriad case.